Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e. neuroticism) and promising biomarker (i.e. amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression

Trait-related neural basis of attentional bias to emotions: a tDCS study

Negative emotional stimuli can strongly bias attention, particularly in individuals with high levels of dispositional negative affect (NA). The current study investigated whether the prefrontal cortex (PFC), a brain region involved in the top-down regulation of emotional processing, plays a different role in controlling attention to emotions, depending on the individual NA. Sham and anodal transcranial direct current stimulation (tDCS) was delivered over the right or left PFC while assessing attentional bias (AB) to emotions (happy, angry, sad faces) in individuals with higher and lower trait NA. When tDCS was inactive (sham), individuals with higher trait NA showed AB toward angry and away from sad faces, while individuals with lower trait NA presented with no AB. Right anodal-tDCS abolished the AB toward angry faces and induced an AB toward sad faces in individuals with higher trait NA, while no effect was found in individuals with lower trait NA. Left anodal-tDCS abolished any AB in individuals with higher trait NA and induced an AB away from happy faces in individuals with lower trait NA. These findings confirm a critical role of trait NA in AB to emotions and demonstrate a different involvement of PFC in emotional processing based on dispositional affect

Neurophysiological, behavioural and genetic markers of behavioural problems in early childhood

The work presented in the present thesis investigated the neural, behavioural and genetic markers that may be associated with the manifestation of behavioural problems during the early years of life. Across four different empirical studies, and by incorporating, behavioural, neurophysiological and genetic investigations, it was demonstrated that: (1) there are neurophysiological signatures that may be associated with the manifestation of behavioural problems early in life; (2) common genetic variations that determine serotonin variability are strongly associated with affectivity-related patterns of frontal brain activation; and that (3) normal genetic variations that modulate serotonin availability and neuroplasticity are each associated with affectivity-related patterns of visual scanning behaviours in response to faces and aversive scenes. Taken together, the results illustrate the existence of robust neural, genetic and behavioural markers that may be associated with the manifestation of behavioural problems in early childhood and prompt further investigation of the area by generating novel hypotheses. Together, the empirical findings of the thesis provide a first stage contribution to the complex mechanisms that may yield risk and resilience for behavioural problems during the early years of life by generating a more comprehensive insight on the field of affectivity

BDNF Val66Met and 5-HTTLPR genotype are each associated with visual scanning patterns of faces in young children

Previous studies have documented both neuroplasticity-related BDNF Val66Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relation to BDNF Val66Met and 5-HTTLPR genotyping in 49 children aged 4- to 7-years. Analyses revealed that variations in the visual processing of facial expressions of anger interacted with BDNF Val66Met genotype, such that children who carried at least one low neuroplasticity Met allele exhibited a vigilance-avoidance pattern of visual scanning compared to homozygotes for the high neuroplasticity Val allele. In a separate investigation of eye gaze towards the eye versus mouth regions of neutral faces, we observed that short allele 5-HTTLPR carriers exhibited reduced looking at the eye region compared with those with the higher serotonin uptake Long allele. Together, these findings suggest that genetic mechanisms early in life may influence the establishment of patterns of visual scanning of environmental stressors, which in conjunction with other factors such as negative life events may lead to psychological difficulties and disorders in the later adolescent and adult years

The Relationship between Anxiety and Task Switching Ability

This study examined task switching ability as a function of anxiety Participants with mild anxiety switched between emotion and age classification among faces There were few important results i Individuals with anxiety categorized facial emotion faster than facial age ii There was a larger switch cost for age than the emotion categorization iii Anxiety was a significant predictor of task switch costs We discussed why anxious individuals showed a deficit in cognitive control of facial attribute

SOCIOECONOMIC STATUS, AMYGDALA REACTIVITY, AND SELECTIVE ATTENTION TO THREAT

In this study, a pathway through which low socioeconomic status (SES) might heighten risk for disorders of mood and affect via a social information-processing bias is investigated. Here, we examined whether measures of social status covary with attentional bias toward threat and with greater threat-related amygdala reactivity in a sample of healthy community volunteers. Participants were middle-aged men and women (30 – 55, M = 42.1 years; 41% female, 87% white) who participated in the second Adult Health and Behavior project (AHAB II). SES indices included objective (individuals’ education and income, parental education) and subjective (individuals rated themselves and their parents on the MacArthur Scale of Subjective Social Status) indicators. Participants’ attentional bias toward threat was assessed using a visual probe-detection task, utilizing angry, fearful, happy, and neutral facial expressions from the Karolinska Directed Emotional Faces stimulus set. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was employed to investigate amygdala reactivity, using facial stimuli derived from the MacArthur Network Face stimulus set. Correlational analyses failed to show any relationship between SES and attentional bias for any of the affective stimuli. Linear regression analyses accounting for age, race, and sex showed lower education (β = -.116, SE = .056, p = .041) and lower composite SES (fear > shapes: β = -.142, SE = .059, p = .018; fear > neutral: β = -.122, SE = .058, p = .037) associated with higher left amygdala reactivity to fearful facial stimuli. No significant relationships between SES and amygdala reactivity were detected for the remaining SES indicators, and findings were limited only to the left amygdala relationship with fearful faces. Thus, our prediction of an inverse association between indices of social standing and heightened responses to threatening stimuli was largely unsupported by the results. Future investigations should include participants representing a broader range of age, ethnicity, and socioeconomic standing in order to more accurately characterize individuals’ responses to threat. Despite the shortcomings of the current study, these findings provide initial (albeit limited) evidence that heightened neurobiological responses to threat may be associated with lower SES

Individual differences in anxiety and automatic amygdala response to fearful faces: A replication and extension of Etkin et al. (2004)

Trait anxiety refers to the stable tendency to attend to threats and experience fears and worries across many situations. According to the widely noticed, pioneering investigation by Etkin et al. (2004) trait anxiety is strongly associated with reactivity in the right basolateral amygdala to non-conscious threat. Although this observation was based on a sample of only 17 individuals, no replication effort has been reported yet. We reexamined automatic amygdala responsiveness as a function of anxiety in a large sample of 107 participants. Besides self-report instruments, we administered an indirect test to assess implicit anxiety. To assess early, automatic stages of emotion processing, we used a color-decision paradigm presenting brief (33 ms) and backward-masked fearful facial expressions. N = 56 participants were unaware of the presence of masked faces. In this subset of unaware participants, the relationship between trait anxiety and basolateral amygdala activation by fearful faces was successfully replicated in region of interest analyses. Additionally, a relation of implicit anxiety with masked fear processing in the amygdala and temporal gyrus was observed. We provide evidence that implicit measures of affect can be valuable predictors of automatic brain responsiveness and may represent useful additions to explicit measures. Our findings support a central role of amygdala reactivity to non-consciously perceived threat in understanding and predicting dispositional anxiety, i.e. the frequency of spontaneously occurring anxiety in everyday life

Neurobiological Mechanisms of Cognitive Processing Therapy for Post-traumatic Stress Disorder: A Brain Network Approach

Psychotherapy research is increasingly targeting both psychological and neurobiological mechanisms of therapeutic change. This trend is evident in and applicable to post-traumatic stress disorder (PTSD) treatment research given the high nonresponse rate of individuals with PTSD who undergo cognitive-behavioral therapy (CBT). A review of the literature investigating neurobiological mechanisms of CBT in PTSD reveals inconsistent results that fail to fully support dual process or learning models of CBT effects in the brain. However, network-based models of psychopathology provide a new framework from which to understand both mental disorder symptoms and therapeutic mechanisms. The current study investigated a) whether brain networks commonly implicated in psychopathology (e.g., default mode network [DMN], central executive network [CEN], and salience network [SN]) changed following Cognitive Processing Therapy (CPT) for PTSD and b) whether change in these networks was associated with PTSD and/or transdiagnostic symptom change. Independent components analysis was implemented to investigate resting-state functional connectivity in DMN, CEN, and SN in 42 women with PTSD and 18 trauma-exposed controls (TEC). Results indicated no significant differences in DMN, CEN, or SN functional connectivity in participants with PTSD versus TEC before or after CPT. Further, participants who completed CPT did not evince significant change in these networks pre- or post-CPT. Several methodological reasons for null results and future directions for research are discussed

Childhood Trauma And Emotion Processing Neurocircuitry

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of observed neurological changes, we evaluate behavioral performance on emotion processing neuropsychological tasks, as well as specific dimensions of subjective affective experience. Results indicate that, relative to matched comparison youth, trauma-exposed youth have (1) increased neural response to salient emotional cues in amygdala and insula, (2) reduced functional connectivity between amygdala and pgACC/sgACC, a pathway critical for emotion regulation, and (3) altered within- and between-network connectivity of the salience network, involved in detecting and orienting attention to salient emotional stimuli. These neurological changes are accompanied by behavioral alterations: trauma-exposed youth have a lower ability to ignore distracting emotional information, and to automatically regulate emotion. Additionally, observed neurobehavioral changes relate to a specific dimension of affective experience – reward sensitivity (RS), rather than negative affect. Moreover, trauma-exposed youth with the greatest neurobehavioral impairment report lower RS, suggesting reduced positive environmental engagement. These results suggest that RS may be a marker of stress susceptibility, a notion supported by emerging basic and clinical research. Based on our neurobehavioral findings, we discuss potential implications for intervention, and relay an emerging framework that dissociates neurological effects of different trauma types (i.e., threat/victimization vs. deprivation/neglect). In closing, we discuss future directions, including longitudinal research and evaluating the modulation of learned fear – a neurobehavioral mechanism that depends on emotion processing neurocircuitry, but has yet to be tested in trauma-exposed youth