Interaction of catechol O-methyltransferase and serotonin transporter genes modulates effective connectivity in a facial emotion-processing circuitry

Imaging genetic studies showed exaggerated blood oxygenation level-dependent response in limbic structures in carriers of low activity alleles of serotonin transporter-linked promoter region (5-HTTLPR) as well as catechol O-methyltransferase (COMT) genes. This was suggested to underlie the vulnerability to mood disorders. To better understand the mechanisms of vulnerability, it is important to investigate the genetic modulation of frontal-limbic connectivity that underlies emotional regulation and control. In this study, we have examined the interaction of 5-HTTLPR and COMT genetic markers on effective connectivity within neural circuitry for emotional facial expressions. A total of 91 healthy Caucasian adults underwent functional magnetic resonance imaging experiments with a task presenting dynamic emotional facial expressions of fear, sadness, happiness and anger. The effective connectivity within the facial processing circuitry was assessed with Granger causality method. We have demonstrated that in fear processing condition, an interaction between 5-HTTLPR (S) and COMT (met) low activity alleles was associated with reduced reciprocal connectivity within the circuitry including bilateral fusiform/inferior occipital regions, right superior temporal gyrus/superior temporal sulcus, bilateral inferior/middle prefrontal cortex and right amygdala. We suggest that the epistatic effect of reduced effective connectivity may underlie an inefficient emotion regulation that places these individuals at greater risk for depressive disorders

Variability in the Effect of 5-HTTLPR on Depression in a Large European Population: The Role of Age, Symptom Profile, Type and Intensity of Life Stressors.

BACKGROUND: Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. METHODS: In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models. RESULTS: The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (</=30) individuals. LIMITATIONS: Our study is cross-sectional and applies self-report questionnaires. CONCLUSIONS: Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups

The Integrative Effects of Cognitive Reappraisal on Negative Affect: Associated Changes in Secretory Immunoglobulin A, Unpleasantness and ERP Activity

Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200–300 ms and 400–1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings

Down-Regulation of Negative Emotional Processing by Transcranial Direct Current Stimulation: Effects of Personality Characteristics

Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study

The Affective Style Questionnaire: Development and Psychometric Properties

Contains fulltext : 90399.pdf (publisher's version ) (Closed access)Affective style is an individual difference variable that refers to tendencies for regulating emotions. The emotion research literature has consistently identified three general strategies to handle emotional reactions: some strategies are aimed at re-adjusting affect to adapt successfully to situational demands; other strategies are intended to conceal or suppress affect; and a third approach is to tolerate and accept emotions, including unwanted and aversive reactions. We conducted two studies to develop a self-report measure to assess these affective styles. In the first study (n = 434), a list of 127 items related to this construct was administered. A factor analysis supported three factors: habitual attempts to conceal or suppress affect (Concealing subscale; 8 items), a general ability to manage, adjust, and work with emotions as needed (Adjusting subscale; 7 items), and an accepting and tolerant attitude toward emotions (Tolerating subscale; 5 items). The scale showed satisfactory internal consistency. Furthermore, the respective subscales showed different patterns of relations with existing instruments measuring similar constructs. Findings were cross-validated in an independent sample (n = 495). The factor structure and results of psychometric analyses were replicated. The final 20-item Affective Style Questionnaire is a brief instrument to measure individual differences in emotion regulation

The Effects of The COMT val108/158met Polymorphism on BOLD Activation During Working Memory, Planning, and Response Inhibition: A Role for The Posterior Cingulate Cortex?

Catechol-O-methyl transferase (COMT) val108/158met polymorphism impacts on cortical dopamine levels and may influence functional magnetic resonance (fMRI) measures of task-related neuronal activity. Here, we investigate whether COMT genotype influences cortical activations, particularly prefrontal activations, by interrogating its effect across three tasks that have been associated with the dopaminergic system in a large cohort of healthy volunteers. A total of 50 participants (13 met/met, 23 val/met, and 14 val/val) successfully completed N-Back, Go-NoGo, and Tower of London fMRI tasks. Image analysis was performed using statistical parametric mapping. No significant relationships between COMT genotype groups and frontal lobe activations were observed for any contrast of the three tasks studied. However, the val/val group produced significantly greater deactivation of the right posterior cingulate cortex in two tasks: the Go-NoGo (NoGo vs Go deactivation contrast) and N-Back (2-back vs rest deactivation contrast). For the N-Back task, the modulated deactivation cluster was functionally connected to the precuneus, left middle occipital lobe, and cerebellum. These results do not support findings of prefrontal cortical modulation of activity with COMT genotype, but instead suggest that COMT val/val genotype can modulate the activity of the posterior cingulate and may indicate the potential network effects of COMT genotype on the default mode network