Baldwin M. Way

Putting Feelings Into Words Affect Labeling Disrupts Amygdala Activity in Response to Affective Stimuli

Putting feelings into words (affect labeling) has long been thought to help manage negative emotional experiences; however, the mechanisms by which affect labeling produces this benefit remain largely unknown. Recent neuroimaging studies suggest a possible neurocognitive pathway for this process, but methodological limitations of previous studies have prevented strong inferences from being drawn. A functional magnetic resonance imaging study of affect labeling was conducted to remedy these limitations. The results indicated that affect labeling, relative to other forms of encoding, diminished the response of the amygdala and other limbic regions to negative emotional images. Additionally, affect labeling produced increased activity in a single brain region, right ventrolateral prefrontal cortex (RVLPFC). Finally, RVLPFC and amygdala activity during affect labeling were inversely correlated, a relationship that was mediated by activity in medial prefrontal cortex (MPFC). These results suggest that affect labeling may diminish emotional reactivity along a pathway from RVLPFC to MPFC to the amygdala.

Neural correlates of dispositional mindfulness during affect labeling.

Objective: Mindfulness is a process whereby one is aware and receptive to present moment experiences. Although mindfulness-enhancing interventions reduce pathological mental and physical health symptoms across a wide variety of conditions and diseases, the mechanisms underlying these effects remain unknown. Converging evidence from the mindfulness and neuroscience literature suggests that labeling affect may be one mechanism for these effects. Methods: Participants (n = 27) indicated trait levels of mindfulness and then completed an affect labeling task while undergoing functional magnetic resonance imaging. The labeling task consisted of matching facial expressions to appropriate affect words (affect labeling) or to gender-appropriate names (gender labeling control task). Results: After controlling for multiple individual difference measures, dispositional mindfulness was associated with greater widespread prefrontal cortical activation, and reduced bilateral amygdala activity during affect labeling, compared with the gender labeling control task. Further, strong negative associations were found between areas of prefrontal cortex and right amygdala responses in participants high in mindfulness but not in participants low in mindfulness. Conclusions: The present findings with a dispositional measure of mindfulness suggest one potential neurocognitive mechanism for understanding how mindfulness meditation interventions reduce negative affect and improve health outcomes, showing that mindfulness is associated with enhanced prefrontal cortical regulation of affect through labeling of negative affective stimuli. fMRI = functional magnetic resonance imaging; PFC = prefrontal cortex; VLPFC = ventrolateral prefrontal cortex; VMPFC = ventromedial prefrontal cortex; MPFC = medial prefrontal cortex; DLPFC = dorsolateral prefrontal cortex.

Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology

BACKGROUND Mixed evidence has suggested that homozygous carriers of the short allele (s/s) of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) may be at increased risk for depression, if they have also been exposed to early or current adversity/stress. We address this debate by examining the relation of a stressful early family environment, recent adversity/stress, and the 5-HTTLPR to depressive symptomatology in a normal sample. METHODS A nonclinical sample of 118 young adult men and women completed assessments of early family environment, recent stressful events, psychosocial resources, and psychological distress, including depressive symptomatology. The 5-HTTLPR was genotyped using a standard protocol with DNA extracted from oral fluid. RESULTS A stressful early family environment was significantly related to depressive symptomatology. In addition, gene-by-environment (GxE) interactions were observed between the 5-HTTLPR and both early family environment and current adversity/stress. Individuals homozygous for the short allele had greater depressive symptomatology if they had experienced early or recent adversity but significantly less depressive symptomatology if they reported a supportive early environment or recent positive experiences, compared with participants with the s/l or l/l genotype. CONCLUSIONS Early or current environment, in conjunction with the serotonin transporter polymorphism, predicts depressive symptomatology.

Neural sensitivity to social rejection is associated with inflammatory responses to social stress

Although stress-induced increases in inflammation have been implicated in several major disorders, including cardiovascular disease and depression, the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown. To examine these processes, we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids. A subset of participants (n = 31) later completed an fMRI session in which their neural responses to social rejection were assessed. As predicted, exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity, namely a soluble receptor for tumor necrosis factor-α (sTNFαRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater increases in sTNFαRII (but not IL-6) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula, brain regions that have previously been associated with processing rejection-related distress and negative affect. These data thus elucidate a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress. As such, they have implications for understanding how social stressors may promote susceptibility to diseases with an inflammatory component.

Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection

Scientific understanding of social pain—the hurt feelings resulting from social rejection, separation, or loss—has been facilitated by the hypothesis that such feelings arise, in part, from some of the same neural and neurochemical systems that generate the unpleasant feelings resulting from physical pain. Accordingly, in animals, the painkiller morphine not only alleviates the distress of physical pain, but also the distress of social separation. Because morphine acts on the μ-opioid receptor, we examined whether variation in the μ-opioid receptor gene (OPRM1), as measured by the functional A118G polymorphism, was associated with individual differences in rejection sensitivity. Participants (n = 122) completed a self-report inventory of dispositional sensitivity to social rejection and a subsample (n = 31) completed a functional MRI session in which they were rejected from an online ball-tossing game played with two supposed others. The A118G polymorphism was associated with dispositional sensitivity to rejection in the entire sample and in the fMRI subsample. Consistent with these results, G allele carriers showed greater reactivity to social rejection in neural regions previously shown to be involved in processing social pain as well as the unpleasantness of physical pain, particularly the dorsal anterior cingulate cortex (dACC) and anterior insula. Furthermore, dACC activity mediated the relationship between the A118G polymorphism and dispositional sensitivity to rejection, suggesting that this is a critical site for μ-opioid-related influence on social pain. Taken together, these data suggest that the A118G polymorphism specifically, and the μ-opioid receptor more generally, are involved in social pain in addition to physical pain.

Understanding Genetic Risk for Aggression: Clues From the Brain's Response to Social Exclusion

BACKGROUND Although research indicates a relationship between the monoamine oxidase-A (MAOA) gene and aggression, the intervening neural and psychological mechanisms are unknown. Individuals with the low expression allele (MAOA-L) of a functional polymorphism in the MAOA gene might be prone to aggression because they are socially or emotionally hyposensitive and thus care less about harming others or because they are socially or emotionally hypersensitive and thus respond to negative social experiences with defensively aggressive behavior. METHODS We investigated the relationships between the MAOA polymorphism, trait aggression, trait interpersonal hypersensitivity, and neural responses to social exclusion in 32 healthy men and women. RESULTS The MAOA-L individuals (men and women) reported higher trait aggression than individuals with the high expression allele (MAOA-H). The MAOA-L individuals reported higher trait interpersonal hypersensitivity and showed greater dorsal anterior cingulate cortex (dACC) activity (associated with rejection-related distress) to social exclusion compared with MAOA-H individuals, consistent with a social hypersensitivity hypothesis. Moreover, the MAOA-aggression relationship was mediated by greater dACC reactivity to social exclusion, suggesting that MAOA might relate to aggression through socioemotional hypersensitivity. CONCLUSIONS These data suggest that the relationship between MAOA and aggression might be due to a heightened rather than a reduced sensitivity to negative socioemotional experiences like social rejection.

Oxytocin receptor gene (OXTR) is related to psychological resources

Psychological resources—optimism, mastery, and self-esteem—buffer the deleterious effects of stress and are predictors of neurophysiological and psychological health-related outcomes. These resources have been shown to be highly heritable, yet the genetic basis for this heritability remains unknown. Here, we report a link between the oxytocin receptor (OXTR) SNP rs53576 and psychological resources, such that carriers of the “A” allele have lower levels of optimism, mastery, and self-esteem, relative to G/G homozygotes. OXTR was also associated with depressive symptomatology. Mediation analysis indicates that the effects of OXTR on depressive symptoms may be largely mediated by the influence of OXTR on psychological resources.

Dispositional Mindfulness and Depressive Symptomatology: Correlations With Limbic and Self-Referential Neural Activity During Rest

To better understand the relationship between mindfulness and depression, we studied normal young adults (n = 27) who completed measures of dispositional mindfulness and depressive symptomatology, which were then correlated with (a) rest: resting neural activity during passive viewing of a fixation cross, relative to a simple goal-directed task (shape-matching); and (b) reactivity: neural reactivity during viewing of negative emotional faces, relative to the same shape-matching task. Dispositional mindfulness was negatively correlated with resting activity in self-referential processing areas, whereas depressive symptomatology was positively correlated with resting activity in similar areas. In addition, dispositional mindfulness was negatively correlated with resting activity in the amygdala, bilaterally, whereas depressive symptomatology was positively correlated with activity in the right amygdala. Similarly, when viewing emotional faces, amygdala reactivity was positively correlated with depressive symptomatology and negatively correlated with dispositional mindfulness, an effect that was largely attributable to differences in resting activity. These findings indicate that mindfulness is associated with intrinsic neural activity and that changes in resting amygdala activity could be a potential mechanism by which mindfulness-based depression treatments elicit therapeutic improvement.

Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity

Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

Early adversity and adult health outcomes

Adversity in childhood has effects on mental and physical health, not only in childhood but across the lifespan. A chief task of our research has been to define the pathways by which childhood experience has these surprising health outcomes, often decades later. The concept of allostatic load, which refers to dysregulations across major biological regulatory systems that have cumulative interacting adverse effects over time, provides a mechanism for understanding these relations and defining specific pathways. To chart these pathways, we examine early childhood socioeconomic status, family environment, and genetic predispositions as antecedents to socioemotional functioning/psychological distress; and neural responses to threat that have downstream effects on major stress regulatory systems, ultimately culminating in risks to mental and physical health outcomes. This integrative approach to investigating the impact of childhood experience on adult health outcomes illustrates the significance of multilevel integrative approaches to understanding developmental psychopathology more generally.