Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between the serotonin transporter promoter polymorphism (5-HTTLPR) and adult unresolved attachment.

Research on antecedents of organized attachment has focused on the quality of caregiving received during childhood. In recent years, research has begun to examine the influence of genetic factors on quality of infant attachment. However, no published studies report on the association between specific genetic factors and adult attachment. This study examined the link between the 5-HTTLPR promoter polymorphism of the serotonin transporter gene and adult unresolved attachment assessed with the Adult Attachment Interview. Genetic material and information on attachment-related loss or trauma were available for 86 participants. Multivariate regression analyses showed an association between the short 5-HTTLPR allele and increased risk for unresolved attachment. Temperament traits and psychological symptoms did not affect the association between 5-HTTLPR and unresolved attachment. The authors hypothesize that the increased susceptibility to unresolved attachment among carriers of the short allele of 5-HTTLPR is consistent with the role of serotonin in modulation of frontal-amygdala circuitry. The findings challenge current thinking by demonstrating significant genetic influences on a phenomenon previously thought to be largely environmentally driven. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Variation in the serotonin transporter gene modulates selective attention to threat.

The 5-HTTLPR is an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene. Prior research has revealed associations between the short-allele variant of this polymorphism, enhanced self-reported negative emotionality, and hypersensitivity of fear relevant neural circuits. In a sample of 50 healthy women we examined the role of 5-HTTLPR for cognitive-affective processing of phylogenetical fear-relevant stimuli (spiders) in a dot probe task. In contrast to homozygote long-allele carriers (ll), participants carrying at least 1 short allele (ss and sl) selectively shifted attention toward pictures of spiders, when these were presented for a duration of 2,000 ms. These results argue for an involvement of 5-HTTLPR in cognitive processing of threatening stimuli and thus, underpin its general role for individual differences in negative affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperlipidaemia and cardiovascular disease

Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression. We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were also differentially distributed in patients and controls (P < 0.03). The SAD patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean +/- s.d. = 15.3 +/- 2.8 vs 17.1 +/- 3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior.     

Serotonin transporter gene associations with psychopathic traits in youth vary as a function of socioeconomic resources.

Although prior research has examined the genetic correlates of antisocial behavior, molecular genetics influences on psychopathic traits remain largely unknown. Consequently, we investigated the influence of polymorphic variation at the serotonin transporter protein gene (SLC6A4) and socioeconomic resources (SES) on psychopathic traits in youth across two distinct samples in two separate studies. In Study 1, a main effect of serotonin transporter (5-HTTLPR) genotype was associated with the impulsivity dimension of psychopathy. That is, individuals homozygous for the short allele evidenced more impulsivity than did those homozygous for the long allele. In contrast, a gene–environment interaction was associated with the callous-unemotional and narcissistic features of psychopathy. Callous-unemotional and narcissistic traits increased as SES decreased only among youths with the homozygous-long (l/l) genotype, a novel finding replicated and extended in Study 2. These studies provide preliminary results that the l/l genotype confers risk for the emotional deficits and predatory interpersonal traits associated with psychopathy among youths raised in disadvantaged environments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective attention to affective stimuli and clinical depression among youths: Role of anxiety and specificity of emotion.

Cognitive models of psychopathology posit that the content or focus of information-processing biases (e.g., attentional biases) is disorder specific: Depression is hypothesized to be characterized by attentional biases specifically for depression-relevant stimuli (e.g., sad facial expressions), whereas anxiety should relate particularly to attentional biases to threat-relevant stimuli (e.g., angry faces). However, little research has investigated this specificity hypothesis and none with a sample of youths. The present study examined attentional biases to emotional faces (sad, angry, and happy compared with neutral) in groups of pure depressed, pure anxious, comorbid depressed and anxious, and control youths (ages 9–17 years; N = 161). Consistent with cognitive models, pure depressed and pure anxious youths exhibited attentional biases specifically to sad and angry faces, respectively, whereas comorbid youths exhibited attentional biases to both facial expressions. In addition, control youths exhibited attentional avoidance of sad faces, and comorbid boys avoided happy faces. Overall, findings suggest that cognitive biases and processing of particular emotional information are specific to pure clinical depression and anxiety, and results inform etiological models of potentially specific processes that are associated with internalizing disorders among youths. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Responding to threat: Hemispheric asymmetries and interhemispheric division of input.

This investigation examined how hemispheric asymmetry and interhemispheric processing contribute to attentional biases toward emotional information. Participants (n?=?88) named the color of lateralized squares presented concurrently with neutral, positive, or threatening words. A left-hemisphere advantage in color naming was reduced when distractors were emotional, suggesting right-hemisphere priming by emotional stimuli. Furthermore, the advantage of dividing the word and color across visual fields was increased for emotion words when they were frequently presented, indicating a strategic use of interhemispheric division of labor to reduce the distracting effect of emotional words. Finally, participants with high levels of anxious apprehension were most likely to make use of this interhemispheric processing strategy, supporting a processing efficiency theory of cognitive function in anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction effect of D4 dopamine receptor gene and serotonin transporter promoter polymorphism on the cortisol stress response.

Genetic variation of the serotonin transporter (SCL6A4, 5-HTT) has been associated with fear- and anxiety-related behaviors, while a polymorphism in exon III of the D4 dopamine receptor gene (DRD4) has been linked to novelty seeking. The dopaminergic and the serotonergic neurotransmitter system have been found to modulate the amygdala-connected circuitries that are crucial in emotional modulation and response to fearful stimuli. Additionally, reactivity of amygdala-innervated effector systems is also essential for our understanding of anxiety-related behaviors. Here, we used the stress-induced activation of the hypothalamic-pituitary-adrenal axis to investigate the impact of 5-HTTLPR and DRD4 on the cortisol stress response in 84 healthy adults. Saliva cortisol was measured during and after the Trier Social Stress Test. We found a significant main effect of DRD4: Carriers of the 7R allele exhibited lower cortisol responses. Additionally, a DRD4 by 5-HTTLPR interaction emerged: 5-HTTLPR LA/LA homozygotes showed a lower cortisol response than did S or LG allele carriers but only if they possessed at least one copy of the DRD4 7R allele. The results point to independent and joint effects of these polymorphisms on stress responsivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

5-HTTLPR status moderates the effect of early adolescent substance use on risky sexual behavior.

Objective: A longitudinal, prospective design was used to investigate a moderation effect in the association between early adolescent substance use and risky sexual behavior 2 years later. A genetic vulnerability factor, a variable nucleotide repeat polymorphism (VNTR) in the promoter region of the serotonin transporter gene SLC6A4, known as 5-HTTLPR, was hypothesized to moderate the link between substance use at age 14 and risky sexual behavior at age 16. This VNTR has been associated with risk-taking behavior. Design: African American youths in rural Georgia (N = 185) provided 2 waves of data on their substance use and sexual behavior. Genetic data were obtained via saliva samples. Main Outcome Measures: Substance use and sexual risk behavior were assessed using youth self-report items developed for this investigation. Results: Multiple regression analyses indicated that the presence of 1 or 2 copies of the short allele of the VNTR interacted with substance use to predict sexual behavior. Substance use had little effect on sexual behavior for youths without the short allele; this effect was greatly increased for youths with the short allele. Conclusion: Genetic vulnerability affected the implications of early onset substance use for later sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating emotion-induced blindness and hypervision.

Previous findings suggest that emotional stimuli sometimes improve (emotion-induced hypervision) and sometimes impair (emotion-induced blindness) the visual perception of subsequent neutral stimuli. We hypothesized that these differential carryover effects might be due to 2 distinct emotional influences in visual processing. On the one hand, emotional stimuli trigger a general enhancement in the efficiency of visual processing that can carry over onto other stimuli. On the other hand, emotional stimuli benefit from a stimulus-specific enhancement in later attentional processing at the expense of competing visual stimuli. We investigated whether detrimental (blindness) and beneficial (hypervision) carryover effects of emotion in perception can be dissociated within a single experimental paradigm. In 2 experiments, we manipulated the temporal competition for attention between an emotional cue word and a subsequent neutral target word by varying cue–target interstimulus interval (ISI) and cue visibility. Interestingly, emotional cues impaired target identification at short ISIs but improved target identification when competition was diminished by either increasing ISI or reducing cue visibility, suggesting that emotional significance of stimuli can improve and impair visual performance through distinct perceptual mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dual-task attention deficits in dysphoric mood.

The attentional functioning of nondysphoric, mildly dysphoric, and moderately to severely dysphoric college students was tested using the attentional blink (AB) paradigm. These groups performed equally well at reporting a single target appearing in a rapidly presented stream of stimuli. All groups showed an AB, with report sensitivity for a 2nd target being reduced when the 2 targets were presented less than 0.5 s apart. Nondysphoric and mildly dysphoric participants showed the same size ABs, but the ABs for moderately to severely dysphoric participants were larger and longer. As predicted, the results showed that moderately to severely dysphoric individuals have attentional impairments. These impairments, however, were evident only in the more demanding dual-task condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of processing emotional stimuli as a function of perceived emotional intelligence, anxiety, and depression.

An individual's self-reported abilities to attend to, understand, and reinterpret emotional situations or events have been associated with anxiety and depression, but it is unclear how these abilities affect the processing of emotional stimuli, especially in individuals with these symptoms. The present study recorded event-related brain potentials while individuals reporting features of anxiety and depression completed an emotion-word Stroop task. Results indicated that anxious apprehension, anxious arousal, and depression were associated with self-reported emotion abilities, consistent with prior literature. In addition, lower anxious apprehension and greater reported emotional clarity were related to slower processing of negative stimuli indexed by event-related potentials (ERPs). Higher anxious arousal and reported attention to emotion were associated with ERP evidence of early attention to all stimuli regardless of emotional content. Reduced later engagement with stimuli was also associated with anxious arousal and with clarity of emotions. Depression was not differentially associated with any emotion processing stage indexed by ERPs. Research in this area may lead to the development of therapies that focus on minimization of anxiety to foster successful emotion regulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parenting moderates a genetic vulnerability factor in longitudinal increases in youths' substance use.

The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of 5HTT (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive parenting would attenuate the link between the 5-HTTLPR polymorphism and longitudinal increases in substance use. African American youths residing in rural Georgia (N = 253, mean age = 11.5 years) provided 4 waves of data on their own substance use; the mothers of the youths provided data on their own parenting practices. Genetic data were obtained from youths via saliva samples. Latent growth curve modeling indicated that 5-HTTLPR status (presence of 1 or 2 copies of the s allele) was linked with increases in substance use over time; however, this association was greatly reduced when youths received high levels of involved-supportive parenting. This study demonstrates that parenting processes have the potential to ameliorate genetic risk. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-guides, autobiographical memory, and anxiety and dysphoria: Toward a cognitive model of vulnerability to emotional distress.

Several aspects of a cognitive model of vulnerability to emotional disorders based on self-discrepancy theory were tested. Anxious, dysphoric, anxious/dysphoric, and control Ss participated in 3 studies over a 4-mo period: screening, assessment of self-guides and self-discrepancies, and an autobiographical memory task in which different types of retrieval cues (including self-guides) were presented, and Ss reported childhood memories as they came to mind. Actual:ideal discrepancy was associated with persistent dysphoria, whereas actual:ought discrepancy was associated with persistent anxiety. Self-guide cues resulted in more efficient retrieval and greater unintended negative emotional content than comparable cue types. The groups were differentiated only by negative affect content in response to self-guide cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective processing of visual alcohol cues in abstinent alcoholics: an approach-avoidance conflict?

When symptomatic individuals selectively attend to emotionally relevant stimuli, the ability to shift attention away from such material is impaired. Subjects may, however, seek to avoid further processing of these stimuli, which would facilitate attentional shifts. This was examined in a group of abstinent alcoholics' responses to stimuli related to alcohol. Eight alcohol and eight neutral words served as cues in a covert attention task. The cues were either valid (2/3 of trials) or invalid (1/3 of trials) indicators of where a response target would appear after 100 or 500 milliseconds. The short interval was expected to interact with an initial approach toward the alcohol word, while the long interval would interact with a subsequent avoidance of the stimulus. As predicted, the alcoholics showed slower reaction times (RTs) to targets invalidly cued by alcohol words in the short interval, reflecting increased difficulties to shift attention. However, the alcoholics demonstrated faster RTs to targets invalidly cued by the alcohol words in the long interval. This indicates that the alcohol cue elicited emotional associations that, subsequent to initial stimulus identification, trigger an interrupting function of the attentional system.     

Congruency, attentional set, and laterality effects with emotional words.

The present study investigated the influence of attention and word-emotion congruency on auditory asymmetries with stimuli that include verbal and emotional components. Words were presented dichotically to 80 participants and were pronounced in either congruent or incongruent emotional tones. Participants were asked to identify the presence of a target word or emotion under 1 of 2 conditions. The blocked condition required detection of a word or emotional target in separate blocks. In the randomized condition, the target was changed across trials by means of a postcue. A right-ear advantage (REA) and a left-ear advantage (LEA) were found for word and emotion targets, respectively. However, the finding of a Condition × Stimulus Type × Ear × Congruency interaction indicated that in the randomized condition, a REA was obtained for words when the stimuli were congruent and a LEA was observed for emotions when the stimuli were incongruent. The findings suggest that randomizing the target reduced the influence of the attentional set established by blocking the target. It is likely that this promoted the detection of hemispheric interference in the randomized condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin transporter (5-HTT) gene variants associated with autism?

An association study was performed to elucidate the role of the serotonin transporter (5-HTT) gene as a susceptibility factor for autism as treatment of patients with antidepressant drugs which selectively target 5-HTT reduced autistic or concomitant symptoms, such as repetitive behavior and aggression, and ameliorate language use. Using the transmission/disequilibrium test (TDT) an analysis was done for a common polymorphism in the upstream regulatory region (5-HTTLPR), a VNTR in intron 2 of the gene and a haplotype of both loci in 52 trios fulfilling stringent criteria for autism and an extended group of 65 trios including patients showing no language delay in their first 3 years of life. A higher frequency and preferential transmission of the long allele of the 5-HTTLPR was observed, but the TDT gave a statistically significant value ( P = 0. 032) only for the extended patient group. This result is in contrast to a recent study by a US group presenting preliminary evidence for preferential transmission of the short allele of 5-HTTLPR in 86 trios. Both studies failed to reveal significant linkage disequilibrium between the VNTR in intron 2 of the gene and autism. In our study haplotype analysis of the 5-HTTLPR and the VNTR in intron 2 supplied evidence for an association of 5-HTT and autism in the stringent ( P = 0.069) and extended patient group ( P = 0.049). Overall, we were not able to replicate the findings of the first study on 5-HTT and autism and instead observed a tendency for association of the opposite genetic variant of the gene with the disorder. The implications for genetic variants of the serotonin transporter in the etiology of autism and possible subgroups of patients, therefore, needs clarification in further studies with other and larger patient samples.     

Attentional capture by emotional stimuli is modulated by semantic processing.

The attentional blink paradigm was used to examine whether emotional stimuli always capture attention. The processing requirement for emotional stimuli in a rapid sequential visual presentation stream was manipulated to investigate the circumstances under which emotional distractors capture attention, as reflected in an enhanced attentional blink effect. Emotional distractors did not cause more interference than neutral distractors on target identification when perceptual or phonological processing of stimuli was required, showing that emotional processing is not as automatic as previously hypothesized. Only when semantic processing of stimuli was required did emotional distractors capture more attention than neutral distractors and increase attentional blink magnitude. Combining the results from 5 experiments, the authors conclude that semantic processing can modulate the attentional capture effect of emotional stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)