Experiential, autonomic, and neural responses during threat anticipation vary as a function of threat intensity and neuroticism.

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses.

Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions.

The study of functionally relevant biological effects of serotonin transporter gene promoter region (5-HTTLPR) polymorphisms is especially important given the current controversy about the clinical relevance of these polymorphisms. Here we report an intrinsic immunobiological difference between individuals carrying two short (SS) versus long (LL) 5-HTTLPR alleles, that is observed in healthy subjects reporting low exposure to life stress. Given that 5-HTTLPR polymorphisms are thought to influence susceptibility to depression and are associated with robust neurobiological effects, that depression is associated with higher pro-inflammatory and lower anti-inflammatory cytokines, and that acute stressors increase circulating concentrations of pro-inflammatory cytokines, we hypothesized that compared to LL individuals, SS individuals may show a pro-inflammatory bias under resting conditions and/or during stress. 15 LL and 11 SS individuals participated in the Trier Social Stress Test (TSST). Serum IL-6 and IL-10 were quantified at baseline and 30, 60, 90, and 120min after beginning the 20-min stress test. Compared to LL individuals, SS individuals showed a higher IL-6/IL-10 ratio at baseline and during stress. Importantly, this pro-inflammatory bias was observed despite both groups being healthy, reporting similar intensities of stress and negative emotionality during the TSST, and reporting similar low exposures to early and recent life stress. To our knowledge, this is the first report of a pro-inflammatory bias/phenotype in individuals carrying the SS genotype of 5-HTTLPR. Thus, healthy SS individuals may be chronically exposed to a pro-inflammatory physiological burden under resting and stress conditions, which could increase their vulnerability to disorders like depression and other diseases that can be facilitated/exacerbated by a chronic pro-inflammatory state.

For better or worse? Stress inoculation effects for implicit but not explicit anxiety.

BACKGROUND: Severe early life stress (ELS) is associated with negative outcomes. It is not clear, however, what impact moderate ELS has. A growing stress inoculation literature suggests that moderate (vs. low or high) ELS is associated with diminished behavioral and physiological anxiety responses. At the same time, studies of trait anxiety suggest that moderate (vs. low) ELS is associated with greater self-reported anxiety. This study tested the hypothesis that stress inoculation effects are evident for implicit (nonconscious) but not explicit (conscious) aspects of anxiety. METHODS: Ninety-seven healthy women were assessed for ELS and explicit anxiety using questionnaires and assessed for implicit anxiety using a version of the Implicit Association Test. RESULTS: Results indicated a quadratic relation between ELS and implicit anxiety, such that moderate ELS was associated with lower implicit anxiety levels than low or high ELS. By contrast, the relation between ELS and explicit anxiety was linear. CONCLUSION: These findings support the stress inoculation hypothesis and suggest that stress inoculation applies for implicit but not explicit aspects of anxiety.

Mindfulness Meditation Training and Self-Referential Processing in Social Anxiety Disorder: Behavioral and Neural Effects.

This study examined the effects of mindfulness-based stress reduction (MBSR) on the brain-behavior mechanisms of self-referential processing in patients with social anxiety disorder (SAD). Sixteen patients underwent functional magnetic resonance imaging while encoding self-referential, valence, and orthographic features of social trait adjectives. Post-MBSR, 14 patients completed neuroimaging. Compared to baseline, MBSR completers showed (a) increased self-esteem and decreased anxiety, (b) increased positive and decreased negative self-endorsement, (c) increased activity in a brain network related to attention regulation, and (d) reduced activity in brain systems implicated in conceptual-linguistic self-view. MBSR-related changes in maladaptive or distorted social self-view in adults diagnosed with SAD may be related to modulation of conceptual self-processing and attention regulation. Self-referential processing may serve as a functional biobehavioral target to measure the effects of mindfulness training.

Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse.

BACKGROUND: According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression. METHODS: Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed. RESULTS: Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state. CONCLUSIONS: These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.

Trait Rumination Is Associated with Enhanced Recollection of Negative Words.

Rumination is associated with Major Depressive Disorder (MDD). To better understand this association, researchers have begun to investigate the relationship between rumination and cognitive biases that are linked to MDD. To date, several studies have found that rumination is related to negatively biased memory, but it is not clear whether this relationship is independent of depressive symptoms. To address this question, the present study examined 97 healthy Caucasian women between the ages of 18 and 25. Participants performed an encoding task of self-referent adjectives, followed by a recognition task. The recognition task utilized a remember/know paradigm to separately examine recollection-based memory and familiarity-based memory. Trait rumination was assessed using the ruminative response scale (RRS). Results indicate that high trait rumination is associated with selective enhancement of recollection for negative words compared to neutral words and a trend toward selective enhancement for recollection for negative words compared to positive words. Trait rumination does not affect biases in overall recognition sensitivity or familiarity.

Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.

OBJECTIVE: Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress. METHOD: An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration. RESULTS: Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele. CONCLUSIONS: These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.

The neural bases of emotion regulation: reappraisal and suppression of negative emotion.

BACKGROUND: Emotion regulation strategies are thought to differ in when and how they influence the emotion-generative process. However, no study to date has directly probed the neural bases of two contrasting (e.g., cognitive versus behavioral) emotion regulation strategies. This study used functional magnetic resonance imaging (fMRI) to examine cognitive reappraisal (a cognitive strategy thought to have its impact early in the emotion-generative process) and expressive suppression (a behavioral strategy thought to have its impact later in the emotion-generative process). METHODS: Seventeen women viewed 15 sec neutral and negative emotion-eliciting films under four conditions--watch-neutral, watch-negative, reappraise-negative, and suppress-negative--while providing emotion experience ratings and having their facial expressions videotaped. RESULTS: Reappraisal resulted in early (0-4.5 sec) prefrontal cortex (PFC) responses, decreased negative emotion experience, and decreased amygdala and insular responses. Suppression produced late (10.5-15 sec) PFC responses, decreased negative emotion behavior and experience, but increased amygdala and insular responses. CONCLUSIONS: These findings demonstrate the differential efficacy of reappraisal and suppression on emotional experience, facial behavior, and neural response and highlight intriguing differences in the temporal dynamics of these two emotion regulation strategies.