Alissa J. Ellis

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.

Association of Predeployment Gaze Bias for Emotion Stimuli With Later Symptoms of PTSD and Depression in Soldiers Deployed in Iraq

OBJECTIVE Biased processing of emotion stimuli is thought to confer vulnerability to psychopathology, but few longitudinal studies of this link have been conducted. The authors examined the relationship between predeployment gaze bias for emotion stimuli and later symptoms of posttraumatic stress disorder (PTSD) and depression in soldiers deployed to Iraq. METHOD An eye-tracking paradigm was used to assess line of gaze in 139 soldiers while they viewed a two-by-two matrix of fearful, sad, happy, and neutral facial expressions before they were deployed to Iraq. Once they were deployed, the soldiers periodically reported on their levels of war zone stress exposure and symptoms of PTSD and depression. RESULTS War zone stress exposure predicted higher scores on PTSD and depression symptom measures; however, eye gaze bias moderated this relationship. In soldiers with war zone stress exposure, shorter mean fixation time when viewing fearful faces predicted higher PTSD symptom scores, and greater total fixation time and longer mean fixation time for sad faces predicted higher depressive symptom scores. CONCLUSIONS Biased processing of emotion stimuli, as measured by gaze bias, appears to confer vulnerability to symptoms of PTSD and depression in soldiers who experience war zone stress.

Serotonin transporter gene promoter region polymorphism and selective processing of emotional images

Several studies have now documented that the serotonin transporter promoter region (5-HTTLPR) polymorphism predicts neural response to affective images in brain regions involved in the experience of emotion. However, the behavioral consequences of this genetic effect are less well known. The current study used eye-tracking methodology to examine how individuals genotyped for the 5-HTTLPR allocated their attention when simultaneously presented an array of positive and negative emotional scenes. Short 5-HTTLPR allele homozygotes displayed a bias to focus on positive images, particularly in the first half of the 30s trial. In contrast, long 5-HTTLPR allele homozygotes viewed the stimuli in a more evenhanded fashion. Thus, short 5-HTTLPR allele homozygotes may be attempting to regulate greater reactivity to negative stimuli by purposefully turning their attention towards positive stimuli. Although this sensitivity may have benefits under benign conditions, it may also increase vulnerability to affective disorders when cognitive resources needed to turn attention away from negative stimuli are compromised.

Attentional Biases and the Persistence of Sad Mood in Major Depressive Disorder

This study examined whether attentional biases for emotional information are associated with impaired mood recovery following a sad mood induction among individuals with and without major depressive disorder (MDD). Attentional biases were assessed with an exogenous cuing task using emotional facial expressions as cues among adults with (n = 48) and without (n = 224) current MDD. Mood reactivity and recovery were measured following a sad mood induction. Mood reactivity strongly predicted mood recovery; however, this relationship was moderated by attentional biases for negative emotional stimuli. Biases for sad and fear stimuli were associated with diminished mood recovery following mood induction across the sample. However, biases for sad stimuli were associated with significantly greater impairments in mood recovery among individuals with MDD than healthy controls. Furthermore, within the MDD group, impaired mood recovery was positively associated with depression severity. These results suggest that attentional biases maintain depression, in part, by facilitating the persistence of sad mood.

Identification of Emotionally Ambiguous Interpersonal Stimuli Among Dysphoric and Nondysphoric Individuals

This study examined whether dysphoria influences the identification of non-ambiguous and ambiguous facial expressions of emotion. Dysphoric and non-dysphoric college students viewed a series of human faces expressing sadness, happiness, anger, and fear that were morphed with each other to varying degrees. Dysphoric and non-dysphoric individuals identified prototypical emotional expressions similarly. However, when viewing ambiguous faces, dysphoric individuals were more likely to identify sadness when mixed with happiness than non-dysphoric individuals. A similar but less robust pattern was observed for facial expressions that combined fear and happiness. No group differences in emotion identification were observed for faces that combined sadness and anger or fear and anger. Dysphoria appears to enhance the identification of negative emotion in others when positive emotion is also present. This tendency may contribute to some of the interpersonal difficulties often experienced by dysphoric individuals.

Effect of antidepressant medication use on emotional information processing in major depression.

OBJECTIVE Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. METHOD The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. RESULTS Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. CONCLUSIONS Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

Parental expressed emotion and suicidal ideation in adolescents with bipolar disorder.

Family environmental variables are risk factors for recurrent courses of mood disorder in adolescents. The present study examined the association between parental expressed emotion (EE)-critical, hostile and/or emotionally overinvolved attitudes toward a concurrently ill offspring-and suicidal ideation in adolescents with bipolar disorder. The sample consisted of 95 adolescents with a bipolar I or II diagnosis who had experienced a mood episode in the prior 3 months. Participants (mean age=15.54 years, S.D.=1.4) were interviewed and completed questionnaires regarding current and past suicidal ideation prior to their participation in a treatment trial. Parents completed five-minute speech samples from which levels of EE were assessed. High EE attitudes in parents were associated with current suicidal ideation in adolescents. This relationship was independent of the effects of age, gender, current depressive or manic symptoms, comorbid diagnoses, bipolar I/II subtypes, family adaptability, and family cohesion. These results underscore the importance of addressing the emotional reactivity of caregivers in treating adolescents with bipolar disorder who have suicidal ideation.

Serotonin transporter promoter region (5‐HTTLPR) polymorphism predicts resting respiratory sinus arrhythmia

Respiratory sinus arrhythmia (RSA) is often conceptualized as an index of physiological flexibility that has been related to emotion regulatory capacity. Although behavioral genetics research indicates that RSA is partly heritable, relatively few molecular genetics studies have been conducted. We examined whether the serotonin transporter promoter region (5-HTTLPR) polymorphism was associated with resting RSA among healthy young adults (N=71). Short 5-HTTLPR allele carriers had significantly lower resting RSA than long 5-HTTLPR homozygotes. Genotype explained 5% of the variance in resting RSA. Although firm conclusions depend on further study, the short allele of the 5-HTTLPR polymorphism may contribute to individual differences in RSA and its behavioral correlates.

5-HTTLPR, HTR1A, and HTR2A cumulative genetic score interacts with mood reactivity to predict mood-congruent gaze bias

Genetic variation within the serotonin system has been associated with biased attention for affective stimuli and, less consistently, with vulnerability for major depressive disorder. In particular, 5-HTTLPR, HTR1A (rs6295), and HTR2A (rs6311) polymorphisms have been linked with biased cognition. The present study developed a serotonergic cumulative genetic score (CGS) that quantified the number of risk alleles associated with these candidate polymorphisms to yield a single CGS. The CGS was then used to model genetic influence on the relationship between reactivity to a negative mood induction and negatively biased cognition. A passive-viewing eye-tracking task was administered to 170 healthy volunteers to assess sustained attention for positive, dysphoric, neutral, and threatening scenes. Participants were then induced into a sad mood and readministered the passive-viewing task. Change in gaze bias, as a function of reactivity to mood induction, was the primary measure of cognitive vulnerability. Results suggest that, although none of the individual genes interacted with mood reactivity to predict change in gaze bias, individuals with higher serotonin CGS were significantly more likely to look toward dysphoric images and away from positive images as mood reactivity increased. These findings suggest that a CGS approach may better capture genetic influences on cognitive vulnerability and reaffirm the need to examine multilocus approaches in genomic research.

Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder

Introduction: Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD‐like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. Method: ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no‐go task—a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. Results: This is the first study in ADHD to demonstrate that the dorsal‐lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400–800 ms after stimulus) predicted a higher number of commission errors throughout the task. Conclusions: These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD. HighlightsGreater frontal asymmetry during failed inhibition distinguished ADHD from healthy youth.ADHD youth with greater frontal asymmetry had a greater number of inhibitory errors.Frontal asymmetry may be a biomarker of cognitive disinhibition among ADHD youth.The dorsal‐lateral prefrontal cortex may be responsible for generating frontal alpha.Findings support conceptualization of ADHD as an approach‐related disorder.