The DRD4 VNTR polymorphism influences reactivity to smoking cues

Recent research has indicated that craving for tobacco can be reliably elicited by exposure to smoking cues, suggesting that cue-elicited craving for tobacco may be a useful phenotype for research on genetic factors related to nicotine dependence. Given the potential role of dopamine in cue-elicited craving, the authors examined whether the DRD4 VNTR polymorphism is associated with cue-elicited craving for tobacco. Participants who were homozygous or heterozygous for the 7 repeat (or longer) allele were classified as DRD4 L, and all other participants were classified as DRD4 S. Participants were exposed to smoking cues before smoking either high-nicotine cigarettes or control cigarettes. Analyses suggested that participants in the L group demonstrated significantly greater craving, more arousal, less positive affect, and more attention to the smoking cues than did the participants in the S group.     

The association between religiosity and alcohol use: the mediating role of meaning in life and media exposure

We examined whether meaning in life and exposure to media mediate the association between religiosity and alcohol use among members of the Jewish-orthodox community in Israel. One hundred and ten young adult men self-identified as orthodox (n?=?57) or secular (n?=?53) participated in the study. Participants completed self-report measures designed to assess meaning in life, media exposure, alcohol use, and craving. Our findings show that orthodox participants consumed less alcohol and reported less alcohol craving compared to their secular counterparts. Importantly, search for meaning in life and media exposure mediated the relationship between religiosity and alcohol craving. Our findings suggest that religion provides a sense of meaning that serves as a protective factor against alcohol craving, supporting existential theories. Furthermore, our studies show that practices that are associated with a religious lifestyle such as low exposure to mass media also serve as protective factors for alcohol use and craving.     

The Dopamine Receptor D4 Gene (<Emphasis Type="Italic">DRD4</Emphasis>) Moderates Family Environmental Effects on ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prime candidate for exploration of gene-by-environment interaction (i.e., G x E), particularly in relation to dopamine system genes, due to strong evidence that dopamine systems are dysregulated in the disorder. Using a G x E design, we examined whether the DRD4 promoter 120-bp tandem repeat polymorphism, previously associated with ADHD, moderated the effects of inconsistent parenting and marital conflict on ADHD or Oppositional-Defiant Disorder (ODD). Participants were 548 children with ADHD and non-ADHD comparison children and their parents. Homozygosity for the DRD4 promoter 120-bp tandem repeat insertion allele increased vulnerability for ADHD and ODD only in the presence of inconsistent parenting and appeared to increase susceptibility to the influence of increased child self-blame for marital conflict on ADHD inattention. DRD4 genotypes may interact with these proximal family environmental risk factors by increasing the individual’s responsivity to environmental contingencies.     

Interaction between the DRD4 VNTR polymorphism and proximal and distal environments in alcohol dependence during emerging and young adulthood

The manifestation of alcohol dependence at different developmental stages may be associated with different genetic and environmental factors. Taking a developmental approach, we characterized interaction between the dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism and developmentally specific environmental factors (childhood adversity, college/Greek organization involvement, and delayed adult role transition) on alcohol dependence during emerging and young adulthood. Prospective data were obtained from a cohort of 234 White individuals (56% women, 44% men) who were followed up at ages 18 through 34. A longitudinal hierarchical factor model was estimated to model a traitlike persistent alcohol dependence factor throughout emerging and young adulthood and 2 residual statelike alcohol dependence factors limited to emerging adulthood and young adulthood, respectively. We accounted for those alcohol dependence factors by modeling 3 two-way interaction effects between the DRD4 VNTR polymorphism and the 3 developmentally specific environment factors. Carriers of the DRD4 long allele showed greater susceptibility to environmental effects; they showed more persistent symptoms of alcohol dependence as childhood adversity increased and more alcohol dependence symptoms limited to emerging adulthood as college/Greek organization involvement increased. Alcohol dependence among noncarriers of the long allele, however, did not differ as a function of those environments. Although replication is necessary, these findings highlight the importance of repeated phenotypic assessments across development and modeling both distal and proximal environments and their interaction with genetic susceptibility at specific developmental stages.     

The Dopamine D4 Receptor (DRD4) Exon 3 VNTR Contributes to Adaptive Personality Differences in an Italian Small Island Population

The search for evolutionary forces shaping the diversity of human personality traits encouraged studies that have found that islanders are relatively closed and introverted, with little interest in the external world. The ‘personality gene flow’ hypothesis was proposed to explain the mechanism underlying this difference, suggesting that the frequency of alleles that influence islander personality traits might progressively increase in the gene pools on islands because of selective emigration of individuals not displaying these alleles. We genotyped 96 individuals from the Italian mainland and 117 from Giglio Island, whose residents were previously assessed regarding their personality traits. We genotyped three polymorphisms: the dopamine D4 receptor (DRD4) exon 3 repeat region, the serotonin‐transporter SLC6A4 5‐HTTLPR indel and the dopamine transporter SLC6A3 DAT1 3′UTR repeat region. Only the DRD4 exon 3 repeat was hypothesised to show varying allele frequencies because this polymorphism could be associated with human migration and personality traits such as extraversion, openness and novelty seeking. As predicted, no differences in allele frequencies were found for the SLC6A4 and SLC6A3 polymorphisms, whereas significant differences were observed in the frequency of the DRD4 exon 3 alleles. The DRD4.2 repeat was more common in mainlanders, as expected, whereas the DRD4.7 allele was over‐represented among islanders who never emigrated. This last result contradicts the suggested association of this allele with long‐distance migrations. We suggest that emigration might have caused gene flow out the island that resulted in somewhat unpredictable changes in the frequencies of specific alleles, thus influencing islander personality traits. Copyright © 2013 European Association of Personality Psychology     

The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors

Abstract

Thanks to the development of molecular genetics methods it is now possible to look for the genes which may contribute to posttraumatic stress disorder (PTSD). Polymorphism located in exon III of dopamine receptor type 4 (DRD4) gene was related to maladaptive stress responses as well as temperament traits related to PTSD. This study analyzed the association between the variable number tandem repeat (VNTR) DRD4 exon III polymorphism and intensity of PTSD symptoms in 107 (57 women and 50 men) survivors of a flood aged 14–62. Intensity of PTSD symptoms was measured using PTSD-F and PTSD-C questionnaires. Multivariate analysis of covariance (MANCOVA) was conducted to test the main and interactive effects of genotype and level of trauma exposure. Participants with at least one copy of the DRD4 long allele (seven or eight repetitions) had more intense PTSD symptoms on the Avoidance/Numbing scale (Cohen's f = .22) and the Total Scale (Cohen's f = .2) of the PTSD-F than participants who did not have these alleles in genotype. The results must be treated with caution, however, due to methodological restrictions and they need to be replicated on a larger sample.     

Randomized controlled trial of brief interventions to reduce college students' drinking and risky sex

The present study tested the proposition that an intervention to reduce alcohol use among college students will also reduce their risky sexual behavior. In a randomized controlled trial, 154 heavy-drinking, predominantly White, heterosexual college students at behavioral risk for infection with HIV and other sexually transmitted diseases were assigned to receive no intervention or a two-session, in-person, motivational interviewing-based intervention focused on (a) reducing alcohol risk behavior, (b) reducing HIV risk behavior, or (c) reducing both alcohol and HIV risk behavior. Three-month retrospective assessments of alcohol use and sexual behavior were conducted at intake and at 3-, 6-, 9-, 12-, and 15-month follow-up appointments. During follow-up, participants who received the single-focus alcohol risk-reduction intervention drank less frequently and consumed fewer drinks per drinking day as compared with no-intervention control participants, but did not differ from control participants in their frequency of intercourse without a condom or number of sexual partners. Participants who received the single-focus HIV risk-reduction intervention evidenced fewer unprotected sex events during follow-up, as compared with control participants. The number of sexual partners reported during follow-up did not differ by condition. Effects of the interventions did not vary significantly over time and were not moderated by participant gender. Results suggest that intervening to reduce alcohol use may not reduce risky sexual behavior among nonminority college students, but that a brief motivational intervention targeting HIV risk behavior may have utility for reducing the frequency of unprotected sex in this population.     

21st birthday drinking and associated physical consequences and behavioral risks

Twenty-first birthday celebrations often involve dangerously high levels of alcohol consumption, yet little is known about risk factors for excessive drinking on this occasion. Participants (N = 150) from a larger prospective study who consumed at least one drink during their celebration completed questionnaires and semistructured interviews about their 21st birthday within four days after the event. Assessments were designed to characterize 21st birthday alcohol use, adjusted for alcohol content, as well as situational/contextual factors (e.g., celebration location, peer influence) that contribute to event-level drinking. Participants reported an average of 10.85 drinks (9.76 adjusted drinks), with experienced drinkers consuming significantly more than relatively na?ve drinkers who had no previous binge or drunken episodes. Men consumed more drinks, whereas age of first drunken episode and heavier drinking during the 3-months preceding the 21st birthday predicted higher estimated blood alcohol concentrations (eBACs) on the 21st birthday. Celebrating in bars and engaging in birthday-specific drinking traditions (free drinks at bars) explained additional variance in 21st birthday eBACs. Both physical consequences (e.g., blacking out or having a hangover) and behavioral risks (e.g., sexually provocative behaviors) were prevalent and were predicted by higher eBACs. Together these findings indicate that 21st birthday celebrations are associated with heavy drinking and a variety of physical consequences and behavioral risks.     

Depressive rumination and the C957T polymorphism of the DRD2 gene

Depressed individuals who ruminate have difficulties learning from punishment and suppressing task-irrelevant information. The C957T polymorphism of the DRD2 gene, which affects functioning of D2 dopamine receptors (DRD2) that are expressed predominantly in the indirect pathway of the basal ganglia, has been found to influence suppression and punishment learning. Given these associations, we examined in the present study whether depressive rumination is related to the C957T polymorphism in 317 clinically depressed individuals and 317 never-depressed control individuals. A 2 × 2 (diagnostic group ×C957T polymorphism) analysis of variance conducted on depressive rumination scores yielded a significant interaction of group and C957T: Individuals with two 957C alleles reported higher levels of depressive rumination than did individuals with one or two 957T alleles if they were depressed, but not if they were healthy. The present findings suggest that the dopaminergic system and DRD2 are related to the frequency of maladaptive rumination in depressed individuals. Thus, DRD2 may be an important target for the pharmacological treatment of depressive rumination.     

Experimental evidence for differential susceptibility: dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers' externalizing behavior in a randomized controlled trial

In a randomized controlled trial we tested the role of genetic differences in explaining variability in intervention effects on child externalizing behavior. One hundred fifty-seven families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior participated in a study implementing Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), with six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline. A moderating role of the dopamine D4 receptor (DRD4) variable-number tandem repeat (VNTR) exon III polymorphism was found: VIPP-SD proved to be effective in decreasing externalizing behavior in children with the DRD4 7-repeat allele, a polymorphism that is associated with motivational and reward mechanisms and Attention Deficit Hyperactivity Disorder (ADHD) in children. VIPP-SD effects were largest in children with the DRD4 7-repeat allele whose parents showed the largest increase in the use of positive discipline. The findings of this first experimental test of (measured) gene by (observed) environment interaction in human development indicate that children may be differentially susceptible to intervention effects depending on genetic differences.     

慢性应激诱导的抑郁大鼠纹状体par-4基因的表达

为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4, par-4)的表达, 及甲基化是否参与par-4基因表达的调控, 将10周龄大鼠随机分为实验组和对照组, 实验组接受慢性温和应激, 对照组不接受实验性处理。于大鼠13周龄时, 采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平, 以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2, DRD2) mRNA表达水平, 免疫印迹法检测纹状体par-4蛋白质表达水平, 用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现, 与对照组大鼠相比, 实验组大鼠漂浮时间延长, 糖水偏爱率降低, 脑纹状体par-4、DRD2 mRNA及par-4蛋白质表达水平均降低, par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为, 并能抑制纹状体par-4基因的表达, 而基因甲基化可能并不参与其调控机制。     

辣食渴求者抑制控制能力的行为和ERP研究

采用事件相关电位(ERP)技术,探讨一般线索Go/Nogo和辣食线索Go/Nogo任务过程中,辣食渴求者和非辣食渴求者的抑制控制能力。（1）行为结果显示,两组被试辣食线索的反应时和错误率无显著差异,均在任务类型上有差异,即对辣食线索的反应更慢;（2）ERP结果显示,在辣食相关线索Go/Nogo任务中辣食渴求者的N2b和P3波幅都显著小于非辣食渴求者,N2a没有差异;在一般线索Go/Nogo任务中,ERP成分没有发现显著差异。结果提示,辣食渴求者只在辣食相关线索的抑制控制能力弱于非辣食渴求者,这可能意味着他们对辣食线索抑制反应的缺失。     

On the molecular genetics of flexibility: The case of task-switching,inhibitory control and genetic variants

The adjustment of behavior to changing goals and environmental constraints requires the flexible switching between different task sets. Cognitive flexibility is an endophenotype of executive functioning and is highly heritable, as indicated by twin studies. Individual differences in global flexibility as assessed by reaction-time measurement in a task-switching paradigm were recently related to a single nucleotide polymorphism in the vicinity of the dopamine d2 receptor gene DRD2. In the present study, we assessed whether the DRD2 gene is related to backward inhibition, a control mechanism that contributes to cognitive flexibility by reducing proactive interference by no longer relevant task sets. We found that carriers of the DRD2 A1+ variant who have a lower striatal dopamine d2 receptor density than A1– carriers show a larger backward inhibition effect. This is in line with previous results demonstrating increased behavioral flexibility in carriers of this genetic variant. The discussion relates the present finding to those of previous studies assessing the neurogenetic foundations of inhibitory control.     

Dopamine receptor D4 gene variation predicts preschoolers' developing theory of mind

Individual differences in preschoolers' understanding that human action is caused by internal mental states, or representational theory of mind (RTM), are heritable, as are developmental disorders such as autism in which RTM is particularly impaired. We investigated whether polymorphisms of genes affecting dopamine (DA) utilization and metabolism constitute part of the molecular basis of this heritability. Seventy-three 42- to 54-month-olds were given a battery of RTM tasks along with other task batteries that measured executive functioning and representational understanding more generally. Polymorphisms of the dopamine D4 receptor gene (DRD4) were associated with RTM performance such that preschoolers with shorter alleles outperformed those with one or more longer alleles. However, polymorphisms of the catechol-O-methyl transferase gene (COMT) and the dopamine transporter gene (DAT1) genes were not associated with children's RTM performance. Further tests showed that the association between DRD4 allele length and RTM performance was not attributable to a common association with executive functioning or representational understanding more generally. We conclude that DRD4 receptors, likely via their effects on frontal lobe development and functioning, may represent a neuromaturational constraint governing the stereotypical and universal trajectory of RTM development.     

The subjective effects of alcohol-tobacco co-use: an ecological momentary assessment investigation

Alcohol and tobacco use covary at multiple levels of analysis, and co-use of the 2 substances may have profound health consequences. To characterize the motivationally relevant processes contributing to co-use, the current study used ecological momentary assessment (EMA) to examine the subjective consequences of naturally occurring simultaneous use of alcohol and tobacco. Current smokers who reported frequently drinking alcohol (N=259) used electronic diaries to monitor their daily experiences for 21 days. Participants responded to prompted assessments and also initiated recordings when they smoked a cigarette or completed the first drink in a drinking episode. Momentary reports of smoking and alcohol consumption were associated with one another, and these effects remained after adjustment for occasion- and person-level covariates. When participants consumed alcohol, they reported increased pleasure and decreased punishment from the last cigarette. Smoking was associated with small increases in pleasure from the last drink. Ratings of buzzed and dizzy were synergistically affected by co-use of alcohol and tobacco. Co-use was also followed by higher levels of craving for both alcohol and tobacco. Results point to the importance of reward and incentive processes in ongoing drug use and suggest that alcohol intensifies real-time reports of the motivational consequences of smoking more strongly than smoking affects corresponding appraisals of alcohol effects.     

Alcohol self‐presentation: the role of impression motivation and impression construction

Two studies examined impression motivation (IM) and impression construction (IC) processes in college freshman alcohol use. In both studies, students completed individual difference measures related to IM and alcohol IC. In Study 1 (n = 232), participants were assigned to IM (low vs. high) and IC (alcohol vs. control) conditions and then created a personal profile. In Study 2 (n = 65), participants reported levels of IM and alcohol IC, and number of drinks during each evening's social interactions for 3 weeks. Situational alcohol IC was positively related to whether participants presented themselves as an alcohol user in their profile (Study 1) and in the amount they drank (Study 2). In Study 2, the association between IC and drinking was moderated by IM.     

Amnesia,folklore and folks: recovered memories in clinical practice

The concepts of loss of control and craving are reveiwed and relevant experimental findings are discussed. Speed of drinking is suggested as a behavioural measure of craving and an experiment is described to test the hypothesis that craving is primed by a moderate dose of alcohol (45 gms). The hypothesis was confirmed but only for the severely dependent alcoholics.     

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。     

Do research assessments make college students more reactive to alcohol events?

This study examines possible synergistic effects of alcohol-related events and postevent assessments on changes in college student readiness to change alcohol use, frequency of alcohol use, and negative consequences. Students were participants in a longitudinal study of drinking behavior. A portion of those reporting negative alcohol events/consequences (e.g., injury, vomiting, memory loss) during the parent study were randomly selected to participate in the present study (n = 492) and randomized to a postevent assessment (n = 296) or a no-assessment control (n = 196). Participants in the postevent assessment group were interviewed soon after their event, and participants in both conditions were interviewed three months after their event. Linear regression models showed higher 3-month readiness to change alcohol use in participants who received a postevent assessment than those who did not. There were reductions in drinking days, heavy drinking days, and further consequences postevent, but no differences by assessment group. However, female participants showed greater reductions in drinking days and heavy drinking days if they were assigned to assessment compared to control. There also was greater postevent reduction in drinking days among assessment group participants with high precollege alcohol severity compared to low precollege alcohol severity. Conversely, participants who reported high aversiveness of their event and were in the control group showed greater reduction in heavy drinking days than those assigned to the assessment group. Findings suggest that college student heavy drinking is reactive to alcohol events, whereas reactivity to postevent assessments may depend on gender, alcohol severity, and event aversiveness. This work highlights the importance of considering possible interactions among extratherapeutic factors in clinical outcome research.     

Delineating potential mechanisms of implicit alcohol cognitions: drinking restraint, negative affect, and their relationship with approach alcohol associations

Problem drinkers may use alcohol to avoid negative mood states and may develop implicit cognitive associations between negative emotional states and reinforcing properties of drinking. It is paradoxical that attempts to control drinking, such as among those high in drinking restraint, may inadvertently increase desire to drink and subsequent alcohol consumption, and this may be exaggerated under times of emotional distress when urges to drink are high. We examined whether individuals who are high on drinking restraint would demonstrate stronger alcohol-related thoughts elicited by stimuli that represent the desire to use alcohol, in response to stronger versus weaker negative mood arousal. Seventy hazardous drinkers completed measurements of drinking restraint, alcohol consumption, and consequences of use. After being randomized to view negative or positive pictures sets, participants completed an Implicit Association Task (IAT) to test differences in the strength of the association between desire to approach or avoid alcohol or water cues, and then a measurement of subjective craving following the IAT. Regression analyses showed that trait restriction not temptation was positively related to IAT scores, after controlling for relevant covariates and explained 7% of the total variance. Trait temptation not IAT predicted subjective craving. Negative affect was unrelated to IAT scores, singly or in conjunction with measures of drinking restraint, contrary to predictions. In sum, implicit alcohol cognitions are related to attempts to restrict drinking not temptation to drink and are less strongly influenced by mood state.