Association between serotonin Cumulative Genetic Score and the Behavioral Approach System (BAS): Moderation by early life environment

The present study investigates if genetic variation in the serotonergic system interacts with early adversity to predict changes in the Behavioral Approach System (BAS), a system that taps into reward processing. In a sample of community adults (N = 236) the influence of single serotonergic candidate polymorphisms on BAS was analyzed, we also examined the aggregate contribution of these genetic variants by creating a Cumulative Genetic Score (CGS). A CGS quantifies an individual’s cumulative risk by aggregating the number of risk alleles across the candidate polymorphisms. After individual gene analysis, three candidate genes rs7305115 (TPH2), rs6311 (HTR2A), and rs6295 (HTR1A) were combined into the CGS. There were no significant interactions between individual candidate polymorphisms and childhood adversity, but the CGS interacted with childhood adversity to explain a significant amount of variance (11.6%) in the BAS. Findings suggest that genetic variations in the serotonergic system in combination with childhood adversity contribute to individual differences in reward sensitivity.     

Association between the HTR2B gene and the personality trait of fun seeking

Previous research reported that a rare serotonin receptor 2B gene (HTR2B) stop codon mutation predisposes subjects to severe impulsivity and novelty seeking. In this study, we expanded this previous work by testing six single nucleotide polymorphisms (SNPs) within the HTR2B gene for potential associations with the behavioral inhibition system (BIS) and the three components of the behavioral approach systems (BAS: fun seeking, drive, and reward responsiveness) in a Han Chinese sample (N = 478). Association analysis for individual SNPs indicated that four of the six SNPs (i.e., rs6437000, rs10194776, rs16827801, and rs1549339) were significantly associated with BAS fun seeking (p = .0003–.0022). Haplotype-based association analysis revealed that fun seeking was positively associated with haplotype A–A–G–A for SNPs rs6437000–rs10194776–rs16827801–rs1549339 (p = .0002), which survived Bonferroni correction. Except for the association between BAS reward responsiveness and rs16827801 (p = .005), no other association was found for BAS drive, BAS reward responsiveness, or BIS. This study provides the first evidence for the involvement of the HTR2B gene in BAS fun seeking. A better understanding of the genetic basis of the BIS and BAS would allow us to develop more effective diagnosis, treatment, and prevention of impulsive behavioral problems.     

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.     

Individual differences in positivity offset and negativity bias: Gender-specific associations with two serotonin receptor genes

Individual differences in the evaluation of affective stimuli, such as the positivity offset and negativity bias may have a biological basis. We tested whether two SNPs (HTR2A; 102T>C and HTR1A; 1019C>G) related to serotonin receptor function, a biological pathway associated with affective regulation, were differentially related to positivity offset and negativity bias for males and females. Participants were 109 cigarette smokers who rated a series of affective stimuli to assess reactions to positive and negative pictures. Gender × genotype interactions were found for both SNPs. Males with the 102T allele showed a greater positivity offset than males with the 102C allele. For females, in contrast, the 1019C allele was associated with a greater positivity offset than the 1019G allele, whereas the 102T allele was associated with a greater negativity bias than the 102C allele. Identifying how gender differences may moderate the effect of serotonin receptor genes on affective information processing may provide insight into their role in guiding behavior and regulating affect.     

Effects of dysphoria and induced negative mood on the processes underlying hindsight bias

Hindsight bias is the tendency to overestimate one’s prior knowledge of facts or events once the actual facts or events are known. Several theoretical frameworks suggest that affective states might influence hindsight bias. Nondysphoric participants (n?=?123, BDI?≤?13) in negative or neutral mood, and dysphoric participants (n?=?19, BDI?>?13) generated and recalled answers to difficult knowledge questions. All groups showed hindsight bias, that is, their recalled estimates were closer to the correct answer when this answer was shown at recall. Multinomial modelling revealed, however, that under dysphoria and induced negative mood different processes contributed to hindsight bias. Dysphoria, but not induced negative mood, was associated with a stronger reconstruction bias, compared with neutral mood. A recollection bias appeared in neutral, but neither in induced negative nor dysphoric mood. These findings highlight differences between the cognitive consequences of dysphoria and induced negative mood.     

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.     

Developing a measure of interpretation bias for depressed mood: An ambiguous scenarios test

The tendency to interpret ambiguous everyday situations in a relatively negative manner (negative interpretation bias) is central to cognitive models of depression. Limited tools are available to measure this bias, either experimentally or in the clinic. This study aimed to develop a pragmatic interpretation bias measure using an ambiguous scenarios test relevant to depressed mood (the AST-D).¹ In Study 1, after a pilot phase (N = 53), the AST-D was presented via a web-based survey (N = 208). Participants imagined and rated each AST-D ambiguous scenario. As predicted, higher dysphoric mood was associated with lower pleasantness ratings (more negative bias), independent of mental imagery measures. In Study 2, self-report ratings were compared with objective ratings of participants’ imagined outcomes of the ambiguous scenarios (N = 41). Data were collected in the experimental context of a functional Magnetic Resonance Imaging scanner. Consistent with subjective bias scores, independent judges rated more sentences as negatively valenced for the high versus low dysphoric group. Overall, results suggest the potential utility of the AST-D in assessing interpretation bias associated with depressed mood.     

Affective forecasting and self-rated symptoms of depression,anxiety, and hypomania: Evidence for a dysphoric forecasting bias

Emerging research has examined individual differences in affective forecasting; however, we are aware of no published study to date linking psychopathology symptoms to affective forecasting problems. Pitting cognitive theory against depressive realism theory, we examined whether dysphoria was associated with negatively biased affective forecasts or greater accuracy. Participants (n=325) supplied predicted and actual emotional reactions for three days surrounding an emotionally evocative relational event, Valentine's Day. Predictions were made a month prior to the holiday. Consistent with cognitive theory, we found evidence for a dysphoric forecasting bias—the tendency of individuals in dysphoric states to overpredict negative emotional reactions to future events. The dysphoric forecasting bias was robust across ratings of positive and negative affect, forecasts for pleasant and unpleasant scenarios, continuous and categorical operationalisations of dysphoria, and three time points of observation. Similar biases were not observed in analyses examining the independent effects of anxiety and hypomania. Findings provide empirical evidence for the long-assumed influence of depressive symptoms on future expectations. The present investigation has implications for affective forecasting studies examining information-processing constructs, decision making, and broader domains of psychopathology.     

Biases in visual orienting to negative and positive scenes in dysphoria: An eye movement study

The study investigated biases for negative information in component processes of visual attention (initial shift vs. maintenance of gaze) in dysphoric and nondysphoric individuals. Eye movements were recorded while participants viewed a series of picture pairs depicting negative, positive, and neutral scenes (each pair presented for 3 s). Biases in initial orienting were assessed from the direction and latency of the initial shift in gaze, whereas biases in the maintenance of attention were assessed from the duration of gaze on the picture that was initially fixated. Results indicated that the dysphoric group showed a significantly greater bias to maintain gaze longer on negative pictures, relative to control pictures, compared with the nondysphoric group. There was no evidence of a dysphoria-related bias in initial shift of orienting to negative cues. Results are consistent with a depression-related bias that operates in the maintenance of attention on negative material.     

Gaze behavior predicts memory bias for angry facial expressions in stable dysphoria

Interpersonal theories suggest that depressed individuals are sensitive to signs of interpersonal rejection, such as angry facial expressions. The present study examined memory bias for happy, sad, angry, and neutral facial expressions in stably dysphoric and stably nondysphoric young adults. Participants' gaze behavior (i.e., fixation duration, number of fixations, and distance between fixations) while viewing these facial expressions was also assessed. Using signal detection analyses, the dysphoric group had better accuracy on a surprise recognition task for angry faces than the nondysphoric group. Further, mediation analyses indicated that greater breadth of attentional focus (i.e., distance between fixations) accounted for enhanced recall of angry faces among the dysphoric group. There were no differences between dysphoria groups in gaze behavior or memory for sad, happy, or neutral facial expressions. Findings from this study identify a specific cognitive mechanism (i.e., breadth of attentional focus) that accounts for biased recall of angry facial expressions in dysphoria. This work also highlights the potential for integrating cognitive and interpersonal theories of depression.     

Influence of dysphoria on positive and negative cognitive reactivity to daily mood fluctuations

We used an experience sampling design to investigate the influence of dysphoria on positive and negative cognitive reactivity. Participants recorded their thoughts and mood four times per day on PDA devices for one week. We hypothesized that those higher in dysphoria would demonstrate a greater increase in negative thinking in response to negative mood, and a weaker increase in positive cognitions in response to positive mood. These hypotheses were largely supported. For those participants who reported higher initial dysphoria, there was a stronger association between negative mood and thinking and a weaker link between positive mood and thinking. Regression analyses indicated that positive and negative cognitive reactivity were independently related to dysphoria, suggesting that they represent distinct processes. Our results highlight the importance of understanding levels of both negative and positive cognitive reactivity and underscore the benefits of assessing mood and cognition with repeated measurements in "real-time," in order to better understand the antecedent effects of mood on thinking.     

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.     

BRIEF REPORT Self‐reference,ambiguity, and dysphoria

The present study examined two aspects of a dysphoric attentional bias: (1) the role of the emotional tone of the stimuli; and (2) the role of self‐referential processing. A total of 40 nondepressed participants were divided into groups of high and low dysphoria and then primed using a series of formal and self‐referent tasks. Word fragments were presented, using a computer. Each word fragment could be completed with either of two solutions: (i) a word primed through a formal learning process: or (ii) a word primed through a self‐referential process. Results indicated that dysphoric participants; (1) showed a bias towards negative information in general; and (2) showed a bias towards using self‐referent words to complete ambiguous word fragments, independent of the emotional tone of the stimuli. The implications of these findings for both the dysphoric self‐concept and cognitive therapy are discussed.     

Abstract recall of a happy memory to repair sad mood in dysphoria: A possible link to negative cognition

The capacity to repair sad mood through the deliberate recall of happy memories has been found to be impaired in dysphoric individuals. Rumination, or adopting an abstract processing mode, has been proposed as a possible mechanism underpinning this effect. In low and high dysphoric participants, we examined the relative consequences of adopting an abstract or concrete processing mode during happy memory recall or engaging in distraction for (1) mood repair and (2) cognitive content. Recalling a happy memory in either an abstract or concrete way resulted in greater happiness than distraction. Engaging in abstract recall of a happy memory resulted in high dysphoric participants generating negative evaluations and negative generalisations. These findings raise the interesting possibility that abstract processing of positive memories has the potential to generate negative cognition.     

Us and them: Mood effects on ingroup projection

Mood states affect judgments in general and intergroup judgments in particular. The aim of the present research was to show that ingroup projection is influenced by affective states in a similar way as ingroup bias. Varying mood states and relevance of the intergroup situation orthogonally, the results supported the hypotheses that positive mood in conjunction with low relevance and negative mood in conjunction with high relevance elicit higher levels of biased prototypicality perceptions compared to the other conditions of the design. Given substantial evidence from previous research that mood in conjunction with perceived relevance moderates motivated versus heuristic processing, we propose that the present results correspond with motivation‐ versus cognition‐based ingroup projection and suggest different processes underlying the phenomenon of relative ingroup prototypicality. Copyright © 2013 John Wiley & Sons, Ltd.     

Assessment of mood states: Biases in single-administration assessments

Rasmussen, Jeffrey, Willingham, and Glover (1994) demonstrated that single-administration values derived from the Profile of Mood States (POMS) were biased estimates oftypical mood state. Like the previous study, the present study investigated whether single-administration POMS scores would be similar to average POMS scores derived from multiple administrations. In addition, in this investigation, single-administration instructions directed respondents to estimatetypical mood over a period of time that coincided with the time and duration of the multiple administrations. Subjects rated mood states during two single-administration settings, one before and one just after a multiple administration period. For both single-administration assessments, subjects rated mood relative to “How you have felt for the past 3 days, including today?” During the multiple-administration assessment, subjects rated mood six times a day for 3 days as prompted by preprogrammed wrist monitors. Results were consistent with earlier findings by identifying the bias in single-administration assessments. Initial single-administration values were significantly higher than both the averaged multiple-administration values and the second single-administration scores. These results support the contention that single-administration values from the POMS may provide biased estimates oftypical mood states.     

Understanding vulnerability for depression from a cognitive neuroscience perspective: A reappraisal of attentional factors and a new conceptual framework

We propose a framework to understand increases in vulnerability for depression after recurrent episodes that links attention processes and schema activation to negative mood states, by integrating cognitive and neurobiological findings. Depression is characterized by a mood-congruent attentional bias at later stages of information processing. The basic idea of our framework is that decreased activity in prefrontal areas, mediated by the serotonin metabolism which the HPA axis controls, is associated with an impaired attenuation of subcortical regions, resulting in prolonged activation of the amygdala in response to stressors in the environment. Reduced prefrontal control in interaction with depressogenic schemas leads to impaired ability to exert attentional inhibitory control over negative elaborative processes such as rumination, leading in turn to sustained negative affect. These elaborative processes are triggered by the activation of negative schemas after confrontation with stressors. In our framework, attentional impairments are postulated as a crucial process in explaining the increasing vulnerability after depressive episodes, linking cognitive and biological vulnerability factors. We review the empirical data on the biological factors associated with the attentional impairments and detail how they are associated with rumination and mood regulation. The aim of our framework is to stimulate translational research.     

Nightmares, Bad Dreams, and Emotion Dysregulation: A Review and New Neurocognitive Model of Dreaming

ABSTRACT— Nightmares—vivid, emotionally dysphoric dreams—are quite common and are associated with a broad range of psychiatric conditions. However, the origin of such dreams remains largely unexplained, and there have been no attempts to reconcile repetitive traumatic nightmares with nontraumatic nightmares, dysphoric dreams that do not awaken the dreamer, or with more normative dreams. Based on recent research in cognitive neuroscience, sleep physiology, fear conditioning, and emotional-memory regulation, we propose a multilevel neurocognitive model that unites waking and sleeping as a conceptual framework for understanding a wide spectrum of disturbed dreaming. We propose that normal dreaming serves a fear-extinction function and that nightmares reflect failures in emotion regulation. We further suggest that nightmares occur as a result of two processes that we term affect load—a consequence of daily variations in emotional pressures—and affect distress—a disposition to experience events with high levels of negative emotional reactivity.     

Effects of Rumination and Mindful Self-Focus Inductions During Daily Life in Patients With Remitted Depression: An Experimental Ambulatory Assessment Study

Rumination has been proposed as an important risk factor for depression, whereas mindful attention is considered a protective form of self-focusing. Experimental studies have demonstrated differential effects of these modes when induced in the lab. However, their impact on daily life processes is poorly understood, particularly in individuals vulnerable to depressive relapses. The aim of our study was to examine short- and longer-term effects of repeated brief rumination and mindful self-focus inductions during daily life on momentary mood, cognitions, and cortisol in patients with remitted depression (rMDD) as well as in healthy individuals, and to identify their potential differential effects in these groups. The study involved repeated short ambulatory inductions of a ruminative or a mindful self-focus during daily life with additional assessments of momentary mood, rumination, self-acceptance, and cortisol over 4 consecutive days in a sample of patients with rMDD (n = 32, ≥2 lifetime episodes, age 19–55 years) and matched healthy controls (n = 32, age 21–54 years). Multilevel models revealed differential immediate effects of the two induction modes on all momentary mood and cognitive outcomes (all p’s < .001), but not on cortisol. Detrimental effects of rumination over mindful self-focus inductions were particularly strong for cognitions in the patient group. Longer-term effects of the inductions over the day were lacking. This study underlines immediate deteriorating effects of an induced ruminative compared to a mindful self-focus on momentary mood and cognitions during daily life in patients with rMDD and in healthy individuals. The observed stronger rumination-related reactivity in patients suggests heightened cognitive vulnerability. Understanding rumination- and mindfulness-based mechanisms of action in real-life settings can help to establish mechanism-based treatment options for relapse prevention in depression.     

The role of TPH2 variant rs4570625 in shaping infant attention to social signals

TPH2, the rate-limiting enzyme in the synthesis of serotonin, has been connected to several psychiatric outcomes. Its allelic variant, rs4570625, has been found to relate to individual differences in cognitive and emotion regulation during infancy with T-carriers of rs4570625 showing a relatively heightened attention bias for fearful faces. A significant gene-environment interaction was also reported with the T-carriers of mothers with depressive symptoms showing the highest fear bias.We investigated these associations in a sample of 8-month old infants (N = 330), whose mothers were prescreened for low/high levels of prenatal depressive and/or anxiety symptoms. Attention disengagement from emotional faces (neutral, happy, fearful, and phase-scrambled control faces) to distractors was assessed with eye tracking and an overlap paradigm. Maternal depressive symptoms were assessed at several time points during pregnancy and postpartum. The mean levels of symptoms at six months postpartum and the trajectories of symptoms from early pregnancy until six months postpartum were used in the analyses (N = 274).No main effect of the rs4570625 genotype on attention disengagement was found. The difference in fear bias between the genotypes was significant but in an opposite direction compared to a previous study. The results regarding the interaction of the genotype and maternal depression were not in accordance with the previous studies.These results show inconsistencies in the effects of the rs4570625 genotype on attention biases in separate samples of infants from the same population with only slight differences in age.