Catechol-O-methyltransferase Val158Met genotype affects neural correlates of aversive stimuli processing

It was previously shown that variation of the catechol-O-methyltransferase (COMT) gene modulates brain activity during the processing of stimuli with negative valence, but not for pleasant stimuli. Here, we tested whether the COMT genotype also modulates the electrophysiological correlates of emotional processing and explored whether the environmental factor of life stress influences this effect. Using the early posterior negativity (EPN) paradigm, event-related brain potentials were measured in 81 healthy individuals during the processing of pictures that evoked emotions of positive and negative valence. As was hypothesized, the COMT genotype affected the EPN amplitudes for unpleasant stimuli, but not for pleasant ones. Specifically, Met/Met carriers respond more sensitively to unpleasant stimuli, as compared with Val/Val carriers. We did not find evidence that life stress moderates the effect of the COMT genotype on emotional stimuli processing.     

Influence of brain-derived neurotrophic factor and catechol O-methyl transferase polymorphisms on effects of meditation on plasma catecholamines and stress

Meditation may show differential effects on stress and plasma catecholamines based on genetic polymorphisms in brain-derived neurotrophic factor (BDNF) and catechol O-methyl transferase (COMT). Eighty adults (40 men, 40 women; mean age 26 years) who practiced meditation regularly and 57 healthy control adults (35 men, 22 women; mean age 26 years) participated. Plasma catecholamines (norepinephrine (NE), epinephrine (E), and dopamine (DA)) concentrations were measured, and a modified form of the Stress Response Inventory was administered. The results were analyzed using two-way analysis of covariance (ANCOVA) with control and meditation subjects, gene polymorphism as factors, and meditation duration as the covariate. Two-way ANCOVA showed a significant interaction between control and meditation subjects, and BDNF Val66Met polymorphism on DA/NE+DA/E (p = 0.042) and NE/E+NE/DA (p = 0.046) ratios. A significant interaction was found for control and meditation subjects with COMT Val158Met polymorphism and plasma NE concentrations (p = 0.009). Post hoc ANCOVA in the meditation group, adjusted for meditation duration, showed significantly higher plasma NE concentrations for COMT Met carriers than COMT Val/Val subjects (p = 0.025). Significant differences of stress levels were found between the control and meditation subjects in BDNF Val/Met (p < 0.001) and BDNF Met/Met (p = 0.003), whereas stress levels in the BDNF Val/Val genotype did not differ between the control and meditation groups. This is the first evidence that meditation produces different effects on plasma catecholamines according to BDNF or COMT polymorphisms.     

Increased parasympathetic activity and ability to generate positive emotion: The influence of the BDNF Val66Met polymorphism on emotion flexibility

Cross-species behavioral research suggests that a single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene (rs6265, Val66Met), influences behavioral inflexibility. This SNP has not yet been linked to variability in emotion-related behaviors, despite broader evidence suggesting an association may be present. This investigation explored the role of the BDNF Val66Met polymorphism in emotion response behaviors measured during a lab-based emotional provocation. Specifically, the influence of BDNF Val66Met in emotion flexibility was explored in a sample of healthy adults (N?=?120), emotion responses were recorded during the emotional provocation on multiple dimensions, in response to emotionally-evocative videos of negative then positive valence. These results suggest that Met carriers exhibit decreased parasympathetic responding, and reduced ability to generate positive emotion, relative to Val homozygotes. These findings are the first to suggest an association between the Met allele and a pattern of responding indicative of emotion inflexibility that might afford greater risk for psychopathology.     

The BDNF Val66Met polymorphism impacts victim's moral emotions following interpersonal transgression

Immoral behaviors make individuals abominate and punish transgressors. Inspired by the associations between the Val66Met polymorphism of brain‐derived neurotropic factor (BDNF) gene and emotional responses following negative events, we investigated whether this polymorphism was also associated moral emotions such as punishment and forgiveness following interpersonal transgression. To do so, we categorized 340 individuals according to the BDNF Val66Met and assessed moral emotions by using 12 hypothetic scenarios in different conditions of intention and interpersonal consequence. The results indicated that this polymorphism was significantly associated with moral aversion and punishment towards transgressors. Victims with the Val/Val genotype expressed less aversion and punishment than the Met carriers, regardless of intention and interpersonal consequence. Moreover, this polymorphism was associated with forgiveness. Victims with the Val/Val genotype expressed more forgiveness than the Met carriers. Taken together, these findings highlight the importance of the BDNF Val66Met to moral emotions.     

The Influence of the BDNF Val66Met Polymorphism on Mechanisms of Semantic Priming: Analyses with Drift-Diffusion Models of Masked and Unmasked Priming

Automatic and strategic processes in semantic priming can be investigated with masked and unmasked priming tasks. Unmasked priming is thought to enable strategic processes due to the conscious processing of primes, while masked priming exclusively depends on automatic processes due to the invisibility of the prime. Besides task properties, interindividual differences may alter priming effects. In a recent study, masked and unmasked priming based on mean response time (RT) and error rate (ER) differed as a function of the BDNF Val66Met polymorphism (Sanwald et al., 2020). The BDNF Val66Met polymorphism is related to the integrity of several cognitive executive functions and might thus influence the magnitude of priming. In the present study, we reanalyzed this data with drift-diffusion models. Drift-diffusion models conjointly analyze single trial RT and ER data and serve as a framework to elucidate cognitive processes underlying priming. Masked and unmasked priming effects were observed for the drift rates ν, presumably reflecting semantic preactivation. Priming effects on nondecision time t0 were especially pronounced in unmasked priming, suggesting additional conscious processes to be involved in the t0 modulation. Priming effects on the decision thresholds a may reflect a speed-accuracy tradeoff. Considering the BDNF Val66Met polymorphism, we found lowered drift rates and decision thresholds for Met allele carriers, possibly reflecting a superficial processing style in Met allele carriers. The present study shows that differences in cognitive tasks between genetic groups can be elucidated using drift-diffusion modeling.     

Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms

Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.     

人类情绪记忆的行为遗传学与神经遗传学研究进展述评

情绪记忆及其增强效应存在广泛的个体差异,这种个体差异可能有其神经与遗传基础。近来的行为遗传学与神经遗传学证实人类ADRA2B基因缺失突变以及BDNF Val66Met基因的多态性与情绪记忆增强及其神经机制的个体差异相联系。本文重点介绍与人类情绪记忆相关的这两种基因,梳理了行为与神经遗传学研究的最新进展,指出未来应关注更多候选基因,并重视多个脑区之间的交互作用;还应使用情绪面孔刺激探索BDNF Val66Met基因多态性对情绪记忆编码和提取的影响等。     

COMT基因Val158Met多态性与抑郁的关系

抑郁的发生具有重要的遗传学基础。COMT基因Val158Met多态性是抑郁的重要候选基因位点。目前有关COMT基因Val158Met多态性与抑郁关系的研究主要采用单基因设计、单基因-环境设计以及多基因-环境设计。有资料显示负性情绪偏向及其相关脑区可能在COMT基因Val158Met多态性与抑郁间起中介作用, 但具体机制仍有待探究。未来研究可以进一步考察被试的种族、年龄和性别等因素对COMT基因Val158Met多态性与抑郁关系的调节作用, 并通过采用多基因-环境设计, 综合运用积极与消极环境指标等措施深入考察负性情绪偏向和相关脑区在COMT基因Val158Met多态性与抑郁间的作用及其机制。     

When Good Feelings Turn Mixed: Affective Dynamics and Big Five Trait Predictors of Mixed Emotions in Daily Life

In this study, we examine how daily life fluctuations in positive affect (PA) and negative afect (NA) relate to mixed emotions—that is, simultaneous positive and negative feelings. We utilised three experience sampling studies (total N = 275), in which participants reported their affect 10 times each day for up to 14 days. Because people generally experience fairly stable moderate levels of PA in daily life, we proposed that mixed emotions would typically occur when NA increases and overlaps with, but does not entirely eliminate, PA. Accordingly, within individuals, we found that mixed emotions in daily life were more strongly predicted by changes in NA and the occurrence of negative events than by changes in PA and positive events. At the between-person level, individuals with more variable NA, more stable PA, and higher trait Neuroticism scores experienced higher average levels of mixed emotions. Further, we found evidence that the average magnitude of NA increases may partially mediate the association between Neuroticism and mixed emotions. We also found that positive predictors of mixed emotions are negative predictors of individuals' within-person PA/NA correlations—that is, affective synchrony. Our findings elucidate trait predictors and affective dynamics of daily life mixed emotions, which appear closely intertwined with NA variability. © 2020 European Association of Personality Psychology     

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD)

Object We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. METHODS: Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. RESULTS: Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. Conclusion Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.     

Consideration of the BDNF gene in relation to two phenotypes: hoarding and obesity

The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive-compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N=301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival "thrifty gene" strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms.     

Predicting the use of corporal punishment: Child aggression,parent religiosity,and the BDNF gene

Corporal punishment (CP) has been associated with deleterious child outcomes, highlighting the importance of understanding its underpinnings. Although several factors have been linked with parents’ CP use, genetic influences on CP have rarely been studied, and an integrative view examining the interplay between different predictors of CP is missing. We focused on the separate and joint effects of religiosity, child aggression, parent's gender, and a valine (Val) to methionine (Met) substitution in the brain‐derived neurotrophic factor (BDNF) gene. Data came from a twin sample (51% male, aged 6.5 years). We used mothers’ and fathers’ self‐reports of CP and religiosity, and the other parent's report on child aggression. Complete data were available for 244 mothers and their 466 children, and for 217 fathers and their 409 children. The random split method was employed to examine replicability. For mothers, only the effect of religiosity appeared to replicate. For fathers, several effects predicting CP use replicated in both samples: child aggression, child sex, religiosity, and a three‐way (GxExE) interaction implicating fathers’ BDNF genotype, child aggression and religiosity. Religious fathers who carried the Met allele and had an aggressive child used CP more frequently; in contrast, secular fathers’ CP use was not affected by their BDNF genotype or child aggression. Results were also repeated longitudinally in a subsample with age 8–9 data. Findings highlight the utility of a bio‐ecological approach for studying CP use by shedding light on pertinent gene‐environment interaction processes. Possible implications for intervention and public policy are discussed.

     

How does mindfulness modulate daily stress response: evidences from ambulatory assessment

Objective: Mindfulness has been found to be associated with less adverse stress response. However, little is known about how mindfulness modulates stress response in the real daily life. The current study investigated the relation between daily stress and negative emotions, and explored a mediational link via perceived loss of control, and moderation by dispositional mindfulness, to better understand this association. Design: A total of 95 college students were recruited to complete a questionnaire and to report on their stress, perceived loss of control and negative emotions in daily life. Main Outcome Measures: Mindful Attention Awareness Scale (MAAS) was used to assess dispositional mindfulness. Stress, perceived loss of control and negative emotions were assessed by ambulatory assessment. Results: Stress was positively related with negative emotions at within-person level. Perceived loss of control mediated the relationship between stress and negative emotions. Furthermore, participants with higher levels of dispositional mindfulness showed an attenuated association between stress and anger, and also attenuated associations between perceived loss of control, and anger and fatigue at within-person level. Conclusion: These findings point to perceived loss of control as an important key factor in daily stress effects. Dispositional mindfulness appears to have beneficial effects in that it attenuates the impact of daily stressors on individuals’ wellbeing. Clinical implications and limitations are discussed.     

特质正念与控制点调节日常生活中知觉压力对消极情绪的影响

考察日常生活中知觉压力对消极情绪的动态影响,检验特质正念的调节作用,并进一步探索正念的调节作用是否在不同控制点的个体中存在差异。共有95名在校大学生完成正念注意觉知量表（MAAS）,罗特控制点量表（LOCS）,并通过动态评估的方式,完成每天2次,持续14天的在日常生活情境中针对知觉压力和消极情绪的密集型追踪测量。多层线性模型结果表明：（1）在个体内水平,个体某一时刻的知觉压力可以显著预测个体下一时刻的消极情绪;（2）个体的正念水平越高,日常生活中知觉压力对消极情绪的预测力越低;（3）个体越倾向于内控,日常生活中知觉压力对消极情绪的预测力越低;（4）个体越倾向于外控,正念对日常生活中知觉压力影响消极情绪的调节作用越强。本研究验证了正念对日常生活中压力反应的保护作用,并提示外控者在面临压力时更有可能从正念中获益。     

MAOA基因T941G多态性与同伴侵害对男青少年早期抑郁的交互作用:COMT基因Val158Met多态性的调节效应

抑郁具有复杂的多基因遗传基础,然而既有研究大多采用单基因以及单基因-环境交互设计(G×E)考察抑郁的遗传机制。以757名男青少年为被试(初次测评时Mage=11.32岁,SD=0.49岁),采用多基因-环境交互(G×G×E)设计,本研究考察了MAOA(monoamine oxidase A,单胺氧化酶A)基因T941G多态性、COMT(catechol-O-methyltransferase,儿茶酚胺氧位甲基转移酶)基因Val158Met多态性与同伴侵害对青少年早期抑郁的影响。结果显示,MAOA基因T941G多态性与同伴侵害交互作用于青少年抑郁,同伴侵害仅显著正向预测G等位基因(而非T等位基因)青少年抑郁。而且,MAOA基因T941G多态性与同伴侵害的交互作用受到COMT基因Val158Met多态性的调节,上述交互作用仅存在于COMT Met等位基因而非Val/Val基因型携带者中。研究结果显示,抑郁的产生与个体差异存在多基因与环境间的复杂交互机制。     

Cognitive control and the COMT Val158Met polymorphism: genetic modulation of videogame training and transfer to task-switching efficiency

The study investigated whether successful transfer of game-based cognitive improvements to untrained tasks might be modulated by preexisting neuro-developmental factors, such as genetic variability related to the catechol-O-methyltransferase (COMT)—an enzyme responsible for the degradation of dopamine. The COMT Val¹⁵⁸Met genotype may differentially affect cognitive stability and flexibility, and we hypothesized that Val/Val homozygous individuals (who possess low prefrontal dopamine levels) show more pronounced cognitive flexibility than Met/-carriers (who possess high prefrontal dopamine levels). We trained participants, genotyped for the COMT Val¹⁵⁸Met polymorphism on playing “Half-Life 2”, a first-person shooter game which has been shown to improve cognitive flexibility. Pre-training (baseline) and post-training measures of cognitive flexibility were acquired by means of a task-switching paradigm. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects and that playing first-person shooter games promotes cognitive flexibility in individuals with a suitable genetic predisposition.     

Changing emotion dynamics: individual differences in the effect of anticipatory social stress on emotional inertia

Emotional inertia-the degree to which people's feelings carry over from one moment to the next-is an important property of the temporal dynamics of emotions. Thus far, emotional inertia has only been examined as a stable, trait-like characteristic. However, internal or external events (e.g., stress) may trigger changes in people's emotion dynamics, particularly among individuals with heightened sensitivity to such events. The current study investigated how emotional inertia is influenced by the anticipation of social stress, and how this effect is moderated by individual differences in depression, self-esteem, and fear of negative evaluation. We measured participants' (n = 71) emotional inertia in daily life using experience sampling before and after experimentally manipulating anticipatory social stress. Consistent with previous research, psychological maladjustment was associated with higher emotional inertia during "normal" daily life. However, when anticipating a socially stressful event, levels of emotional inertia dropped, particularly among participants scoring high on depression and fear of negative evaluation and low on self-esteem. These results demonstrate that emotion dynamics can vary as a function of contextual factors and identify moderators of such variation.     

Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion Syndrome.

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.     

Social anxiety and emotion regulation in daily life: spillover effects on positive and negative social events

To minimize the possibility of scrutiny, people with social anxiety difficulties exert great effort to manage their emotions, particularly during social interactions. We examined how the use of two emotion regulation strategies, emotion suppression and cognitive reappraisal, predict the generation of emotions and social events in daily life. Over 14 consecutive days, 89 participants completed daily diary entries on emotions, positive and negative social events, and their regulation of emotions. Using multilevel modeling, we found that when people high in social anxiety relied more on positive emotion suppression, they reported fewer positive social events and less positive emotion on the subsequent day. In contrast, people low in social anxiety reported fewer negative social events on days subsequent to using cognitive reappraisal to reduce distress; the use of cognitive reappraisal did not influence the daily lives of people high in social anxiety. Our findings support theories of emotion regulation difficulties associated with social anxiety. In particular, for people high in social anxiety, maladaptive strategy use contributed to diminished reward responsiveness.     

Effects of Comt Genotype on Behavioral Symptomatology in the 22q11.2 Deletion Syndrome

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val^158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.