Associations between serotonin transporter gene promoter region (5-HTTLPR) polymorphism and gaze bias for emotional information

The serotonin transporter promoter region polymorphism (5-HTTLPR) is associated with neural response to negative images in brain regions involved in the experience of emotion. However, the behavioral implications of this sensitivity have been studied far less extensively. The current study used eye-tracking methodology to examine how individuals genotyped for the 5-HTTLPR, including the single nucleotide polymorphism (SNP) rs25531, allocated attention during prolonged (30-s) exposure to face stimuli depicting positive and negative emotion. Short 5-HTTLPR allele carriers and carriers of the long allele with guanine at the sixth nucleotide (S/LG) displayed a stronger gaze bias (total fixation time, number of fixations, mean fixation length) for positive than for sad, threat, or neutral stimuli. In contrast, those homozygous for the long 5-HTTLPR allele with adenine at the sixth nucleotide (LA) viewed the emotion stimuli in an unbiased fashion. Time course analyses indicated no initial 5-HTTLPR group differences; however, S/LG 5-HTTLPR allele carriers were more likely than LA 5-HTTLPR homozygotes to direct gaze toward happy than toward sad stimuli over time. This bias toward positive stimuli during the later stages of information processing likely reflects a strategic effort to downregulate heightened reactivity to negative stimuli among 5-HTTLPR S/LG allele carriers.     

Serotonin transporter genetic variation and biased attention for emotional word stimuli among psychiatric inpatients

The short allele in a variable repeat sequence of the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with stronger activation in brain regions critical for processing emotional stimuli. The authors examined whether variants of the 5-HTTLPR promoter polymorphism were also associated with individual differences in attentional biases for emotional stimuli. Words related to anxious and dysphoric emotional states were presented to psychiatric inpatients in a standard dot-probe reaction time task. Compared with participants with two long alleles, carriers of the short 5-HTTLPR allele exhibited a stronger attentional bias for anxious word stimuli. No genetic group difference was observed for dysphoric word stimuli. Findings from this preliminary study highlight the potential for integrating genetic and cognitive models of psychopathology.     

Genetic moderation of sensitivity to positive and negative affect in marriage

Hypothesizing that genetic factors partially govern sensitivity to interpersonal cues, we examined whether a polymorphism (5-HTTLPR) in the serotonin transporter gene would moderate spouses' sensitivity to positive and negative partner affect. Before and after marital discussions, participants from 76 couples (total n = 150) reported their affective states. Spouses carrying the short allele of the 5-HTTLPR were more responsive to their partner's preinteraction positive affect and anxiety/nervousness, compared with spouses with two long alleles. These data support the contention that the serotonin system influences affective responses to social stimuli. In contrast to the view that the 5-HTTLPR primarily affects response to adverse experiences, these results suggest that this polymorphism moderates sensitivity to positive as well as negative affect.     

The serotonin transporter promoter polymorphism and childhood positive and negative emotionality

Association studies of the serotonin transporter promoter polymorphism (5-HTTLPR) and negative emotionality (NE) are inconclusive. However, emerging evidence suggests that the association between this polymorphism and NE may be influenced by levels of another temperament trait, positive emotionality (PE). Therefore, this study examined whether the association between the 5-HTTLPR and NE was moderated by PE. A community sample of 413 three-year-old children completed a standardized battery of laboratory tasks designed to tap temperamental emotionality. Children were also genotyped for the 5-HTTLPR. No direct association between 5-HTTLPR genotype and NE was found. However, the interaction of child PE and NE predicted 5-HTTLPR genotype. Furthermore, children with a short allele who were also low in PE had significantly greater NE than children without a short allele or children with high PE. Our findings suggest that the short allele of the 5-HTTLPR is associated with NE only in the context of low PE. Inconsistent links between NE and this gene in previous research may stem from the failure to consider other temperament traits that moderate associations.     

Behavioral inhibition and triallelic genotyping of the serotonin transporter promoter (5-HTTLPR) polymorphism

To examine the genetic bases of the behavioral inhibition system (BIS) and the behavioral approach system (BAS), we evaluated the association between the BIS, the BAS, and a functional length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) in an unscreened sample of undergraduates (N = 211); analyses were conducted using a two-variant (i.e., biallelic) genotyping and three-variant (i.e., triallelic) genotyping of the 5-HTTLPR polymorphism. People with one or two copies of the low-expressing alleles reported stronger endorsement of the BIS than people who were homozygous for the high-expressing alleles; this association was found for triallelic but not biallelic genotyping of the 5-HTTLPR polymorphism. There was no association between the 5-HTTLPR polymorphism and the BAS scales.     

Some animal specific fears are more specific than others: Evidence from attention and emotion measures

Using a visual search methodology we investigated the effect of feared animal stimuli on attention. Our results confirmed the important role of emotion on attention. All participants detected fear-relevant stimuli (snakes and spiders) faster than neutral (mushrooms) ones against a background of fruits. In addition, spider fearful participants were sensitized specifically to detect their feared stimulus (spiders), compared to their fear-relevant but non-feared (snakes) and neutral stimuli. However, for participants fearful of snakes there was no significant difference in detection latencies between the feared (snakes) and the fear-relevant but non-feared animal stimuli (spiders). The results from the attention task were mirrored in the emotional ratings, which showed that spider fear was highly specific, whereas snake fear was associated with a more generalized enhanced evaluation of all negative stimuli.     

Automatic attention does not equal automatic fear: preferential attention without implicit valence

Theories of nonassociative fear acquisition hold that humans have an innate predisposition for some fears, such as fear of snakes and spiders. This predisposition may be mediated by an evolved fear module (Ohman & Mineka, 2001) that responds to basic perceptual features of threat stimuli by directing attention preferentially and generating an automatic fear response. Visual search and affective priming tasks were used to examine attentional processing and implicit evaluation of snake and spider pictures in participants with different explicit attitudes; controls (n = 25) and snake and spider experts (n = 23). Attentional processing and explicit evaluation were found to diverge; snakes and spiders were preferentially attended to by all participants; however, they were negative only for controls. Implicit evaluations of dangerous and nondangerous snakes and spiders, which have similar perceptual features, differed for expert participants, but not for controls. The authors suggest that although snakes and spiders are preferentially attended to, negative evaluations are not automatically elicited during this processing.     

Serotonin transporter (5-HTTLPR) genotype, childhood abuse, and suicide attempts in adult psychiatric inpatients

There is growing evidence that a functional polymorphism in the serotonin transporter gene (5-HTTLPR) moderates the impact of negative life events (e.g., childhood abuse) on the development of depression. However, it is unclear whether the gene x environment interaction predicts suicide attempts specifically. In addition, previous studies have not examined different forms of childhood abuse separately. In the current study, we found that 5-HTTLPR genotype moderated the link between childhood physical and sexual, but not emotional, abuse and adult psychiatric inpatients' histories of suicide attempts.     

不受知觉负载调节的注意捕获效应：生态信息的作用

快速探测到环境中具有生态意义的信息是适应性行为的一种重要表现。本研究采用注意捕获范式检验具有生态意义的信息是否能够被注意系统自动化加工。具体而言, 我们考察对负性面孔中的生态意义信息的加工是否受任务和知觉负载的影响。在实验一中, 我们发现负性面孔相对于中性面孔在高低知觉负载下的注意捕获能力没有显著差异, 表明负性面孔在高低负载下都具有加工优先性。为了分离刺激突显性与生态意义二个因素对实验结果的影响, 在实验二中, 我们将负性面孔刺激替换为具有突显性但不含有生态信息的颜色块刺激, 发现颜色块在高知觉负载下的注意捕获效应显著低于低负载, 即知觉负载能够显著影响其注意捕获能力, 表明负性面孔在实验一中的效应应归因于其本身携带的生态信息。由此, 本研究展示了具有生态意义的视觉刺激能够得到视觉系统的自动化加工。     

Attention control: Relationships between self-report and behavioural measures,and symptoms of anxiety and depression

Previous research has demonstrated differences in processing between fear-relevant stimuli, such as snakes and spiders, and non-fear-relevant stimuli. The current research examined whether non-fear-relevant animal stimuli, such as dogs, birds and fish, were processed like fear-relevant stimuli following aversive learning. Pictures of a priori fear-relevant animals, snakes and spiders, were evaluated as negative in affective priming and ratings and were preferentially attended to in a visual search task. Pictures of dogs, birds and fish that had been trained as CS+ in an aversive conditioning design were evaluated more negatively and facilitated dot probe detection relative to CS? pictures. The current studies demonstrated that stimuli viewed as positive prior to aversive learning were negative and were preferentially attended to after a brief learning episode. We propose that aversive learning may provide a mechanism for the acquisition of stimulus fear relevance.     

5-HTTLPR X Stress in Adolescent Depression: Moderation by MAOA and Gender

Depression surges in adolescence, especially among girls. Most evidence indicates that the short allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) interacts with stress to influence the onset of depression. This effect appears to be less robust in adolescents, particularly among boys, and may be moderated by other genetic polymorphisms. Seeking to explain the adolescent gender difference in depression, this study examined the effects of 5-HTTLPR (rs25531), the monoamine oxidase A-upstream variable number tandem repeat (MAOA-uVNTR), and negative life events (NLE). A community-based longitudinal sample of 309 adolescents reported depressive symptoms and NLE at ages 11, 13, and 15. 5-HTTLPR and MAOA-uVNTR genotypes were ascertained via buccal swabs. A significant four-way interaction of 5-HTTLPR, MAOA-uVNTR, NLE at age 13, and gender predicted depressive symptoms at age 15. Girls were most likely to exhibit elevated depressive symptoms when experiencing NLE if they possessed low-expression MAOA-uVNTR alleles and short 5-HTTLPR alleles, whereas low-expression MAOA-uVNTR alleles but long 5-HTTLPR alleles were implicated in boys. The results indicate that the commonly reported 5-HTTLPR by stress interaction for depression may be limited to individuals with low-expression MAOA-uVNTR alleles. These data also provide new evidence that the short allele of 5-HTTLPR confers susceptibility to stress differently for females compared with males.     

Children's 5-HTTLPR genotype moderates the link between maternal criticism and attentional biases specifically for facial displays of anger

Theorists have proposed that negative experiences in childhood may contribute to the development of experience-specific information-processing biases, including attentional biases. There are also clear genetic influences on cognitive processes, with evidence that polymorphisms in specific candidate genes may moderate the impact of environmental stress on attentional biases (e.g., a functional polymorphism in the serotonin transporter gene; 5-HTTLPR). In the current study, we tested a gene×environment (G×E) model of risk for attentional biases. We hypothesised that children whose mothers exhibit high levels of expressed emotion criticism (EE-Crit) would display attentional biases specifically for angry, but not happy or sad, faces, and that this link would be stronger among children carrying one or two copies of the 5-HTTLPR short allele than among those homozygous for the long allele. Results generally supported these hypotheses, though we found that carriers of the 5-HTTLPR short allele who also had a critical mother exhibited attentional avoidance of angry faces rather than preferential attention.     

Threat-relevance impairs executive functions: negative impact on working memory and response inhibition

The effects of emotional stimulus content on attention are well-known. In contrast, the impact of emotional information on higher executive control functions is undetermined. To elucidate the role of negative emotion in cognitive control, 56 adult female participants performed a combined working memory and response inhibition task, with threat-relevant (spider and snake) and neutral (flower and mushroom) stimuli. Threat-relevant stimuli impaired performance, by causing prolonged response times to working memory items and increased response inhibition error rate relative to neutral stimuli. The impaired response inhibition was only evident when threat-relevant stimuli co-occurred with working memory matches, in line with a common resource pool view of executive functions and emotion processing. Individual differences in reported fear of spiders were associated with differences of inhibitory control, while fear of snakes was associated with impaired overall accuracy on working memory trials. The results are discussed in relation to the dual-competition framework for interaction between executive functions and emotion (Pessoa, 2009).     

Dysfunctional attitudes and the serotonin transporter promoter polymorphism (5-HTTLPR)

Dysfunctional attitudes may be one phenotype by which genes increase risk for depression. Building on research demonstrating associations between serotonin abnormalities and dysfunctional attitudes, we examined the covariation between dysfunctional attitudes and the serotonin transporter gene-linked polymorphic region (5-HTTLPR). In a sample of nondepressed young adults (N = 131), people with one or two copies of the low-expressing alleles reported stronger endorsement of dysfunctional attitudes regarding performance evaluation than people who were homozygous for the high-expressing alleles; there was no association between the 5-HTTLPR polymorphism and dysfunctional attitudes regarding approval by others. These results add to the literature linking the 5-HTTLPR polymorphism and cognitive vulnerabilities for depression.     

5-HTTLPR、性别、家庭社会经济地位与面孔表情识别的关系

该研究采用531名中国汉族健康大学生为被试,综合考察了5-HTTLPR(5-羟色胺转运体基因连锁多态区)基因型、性别和家庭社会经济地位之间交互作用与面孔表情识别的关系。研究结果发现,性别和家庭社会经济地位在面孔表情识别上有显著的主效应。总体来说,家庭社会经济地位较高和女性的被试具有较好的面孔表情识别能力。5-HTTLPR基因型、性别、家庭社会经济地位,它们在面孔表情识别上的三因素交互作用也显著。该三因素交互作用主要是源于,在高家庭社会经济地位背景下,女性携带有5-HTTLPR长片段等位基因比短片段纯合子表现出稍差的面孔表情识别能力。该结果体现了基因与环境多因素交互作用对面孔表情识别能力的重要性。     

Association of serotonin transporter promoter gene polymorphism with violence: relation with personality disorders, impulsivity, and childhood ADHD psychopathology

There is evidence that disturbances in central serotonin (5-HT) function have a role in impulsive aggression, violence, and criminality. A deletion/insertion polymorphism within the 5-HT transporter (5-HTT) promoter gene (5-HTT gene-linked polymorphic region, 5-HTTLPR) is thought to be associated with several psychopathological phenotypes related to disturbed impulse control, anxiety and depression. This study examined the association of the 5-HTTLPR with violent behavior in a sample of 153 male Caucasians referred for a forensic psychiatric examination. We found a significant excess of the short (s) allele and the s/s genotype in patients characterized by recurrent and overt physical violent behavior. This genetic variance explained 5% of the variance of violent behavior. When controlled for the impact of several psychopathologies related to violent behavior, this association was observed in individuals with a history of childhood attention deficit/hyperactivity disorder (ADHD)-related symptoms, but not presenting with personality disorder or increased impulsiveness. In conclusion, the results (i). suggest an association between serotonergic dysfunction and violent behavior, (ii). provide evidence for an-at least partial-genetic regulation of violent behavior in a subgroup of male offenders, and (iii). suggest a significant role for 5-HT transporter functionality for violent behavior.     

Attentional bias to pictures of fear-relevant animals in a dot probe task

Attentional bias to fear-relevant animals was assessed in 69 participants not preselected on self-reported anxiety with the use of a dot probe task showing pictures of snakes, spiders, mushrooms, and flowers. Probes that replaced the fear-relevant stimuli (snakes and spiders) were found faster than probes that replaced the non-fear-relevant stimuli, indicating an attentional bias in the entire sample. The bias was not correlated with self-reported state or trait anxiety or with general fearfulness. Participants reporting higher levels of spider fear showed an enhanced bias to spiders, but the bias remained significant in low scorers. The bias to snake pictures was not related to snake fear and was significant in high and low scorers. These results indicate preferential processing of fear-relevant stimuli in an unselected sample.     

Negative cognitive response to a sad mood induction: Associations with polymorphisms of the serotonin transporter (5-HTTLPR) gene

Increased negative thinking in response to sad mood states has been identified as a marker of depression risk. The present study examined whether polymorphisms of the serotonin transporter (5-HTTLPR) gene were associated with the tendency to endorse negative cognition after sad or neutral mood inductions in a healthy college student sample. Non-depressed participants were genotyped for the 5-HTTLPR and then viewed films designed to elicit a sad mood (n=30) or a neutral mood (n=23). Analyses indicated that individuals homozygous for the short 5-HTTLPR allele endorsed more negative cognition following a sad mood induction than individuals homozygous for the long 5-HTTLPR allele. Negative cognition did not vary as a function of 5-HTTLPR genetic status in the neutral mood condition. These preliminary results suggest that genetic variation of the serotonin transporter may contribute to depression vulnerability via a tendency to think more negatively in response to events that elicit sad mood.     

5-HTTLPR与抑郁相关性的研究动态

摘 要 5-HTTLPR是5-羟色胺转运蛋白基因启动子区域上的多态性位点,对其转录效率具有调节作用。5-HTTLPR基因型与抑郁存在相关,但必须把二者的关系置于一个多基因与环境交互作用的框架下考察。一方面,环境因素的作用不容忽视：S等位基因携带者暴露于负性生活事件时,表现出更多情绪问题,更易发生抑郁。另一方面,CYP2C9、BDNF等基因与5-HTTLPR有交互作用,共同影响抑郁的发生。此外,年龄、性别等因素会对研究结果造成混淆。未来研究应侧重于对机制的探讨。     

Fear and the amygdala: manipulation of awareness generates differential cerebral responses to phobic and fear-relevant (but nonfeared) stimuli

Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing.