Lisa J. Burklund

Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: A small randomized controlled trial

Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N = 40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35) = 7.86, p = .008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33) = 3.39, p = .075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults.

Neural Bases of Moderation of Cortisol Stress Responses by Psychosocial Resources

Psychosocial resources have been tied to lower psychological and biological responses to stress. The present research replicated this relationship and extended it by examining how differences in dispositional reactivity of certain neural structures may underlie this relationship. Two hypotheses were examined: (a) psychosocial resources are tied to decreased sensitivity to threat and/or (b) psychosocial resources are associated with enhanced prefrontal inhibition of threat responses during threat regulation. Results indicated that participants with greater psychosocial resources exhibited significantly less cortisol reactivity following a stress task, as predicted. Analyses using functional magnetic resonance imaging revealed that psychosocial resources were associated with greater right ventrolateral prefrontal cortex and less amygdala activity during a threat regulation task but were not associated with less amygdala activity during a threat sensitivity task. Mediational analyses suggest that the relation of psychosocial resources to low cortisol reactivity was mediated by lower amygdala activity during threat regulation. Results suggest that psychosocial resources are associated with lower cortisol responses to stress by means of enhanced inhibition of threat responses during threat regulation, rather than by decreased sensitivity to threat.

The face of rejection: rejection sensitivity moderates dorsal anterior cingulate activity to disapproving facial expressions.

Abstract Previous research has examined neural responses to threatening facial expressions such as those displaying anger, fear, and disgust. Here, we examined neural responses to a different type of threatening facial expression that primarily signifies a threat to social connection, namely a “disapproving” facial expression. We hypothesized that neural responses to disapproving facial expressions would be moderated by individual differences in rejection sensitivity. Using functional magnetic resonance imaging (fMRI), we scanned participants while they viewed brief video clips of facial expressions depicting disapproval, anger, and disgust. As expected, all three expressions yielded bilateral amygdala activation relative to a resting baseline. Additionally, individuals who scored higher on a measure of rejection sensitivity exhibited greater dorsal anterior cingulate cortex activity in response to disapproving facial expressions, but not in response to anger or disgust facial expressions. Results suggest that, at the neural level, individuals high in rejection sensitivity may be more sensitive to facial expressions signaling potential rejection, but not to threatening facial expressions in general. Results also suggest that disapproving facial expressions convey a distinct type of threat and should be considered in future studies of socially threatening facial expressions.

Randomized controlled trial of cognitive behavioral therapy and acceptance and commitment therapy for social phobia: outcomes and moderators

OBJECTIVE Cognitive behavioral therapy (CBT) is an empirically supported treatment for social phobia. However, not all individuals respond to treatment and many who show improvement do not maintain their gains over the long-term. Thus, alternative treatments are needed. METHOD The current study (N = 87) was a 3-arm randomized clinical trial comparing CBT, acceptance and commitment therapy (ACT), and a wait-list control group (WL) in participants with a diagnosis of social phobia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). Participants completed 12 sessions of CBT or ACT or a 12-week waiting period. All participants completed assessments at baseline and posttreatment, and participants assigned to CBT and ACT also completed assessments 6 and 12 months following baseline. Assessments consisted of self-report measures, a public-speaking task, and clinician ratings. RESULTS Multilevel modeling was used to examine between-group differences on outcomes measures. Both treatment groups outperformed WL, with no differences observed between CBT and ACT on self-report, independent clinician, or public-speaking outcomes. Lower self-reported psychological flexibility at baseline was associated with greater improvement by the 12-month follow-up in CBT compared with ACT. Self-reported fear of negative evaluation significantly moderated outcomes as well, with trends for both extremes to be associated with superior outcomes from CBT and inferior outcomes from ACT. Across treatment groups, higher perceived control and extraversion were associated with greater improvement, whereas comorbid depression was associated with poorer outcomes. CONCLUSIONS Implications for clinical practice and future research are discussed.

The common and distinct neural bases of affect labeling and reappraisal in healthy adults

Emotion regulation is commonly characterized as involving conscious and intentional attempts to change felt emotions, such as, for example, through reappraisal whereby one intentionally decreases the intensity of ones emotional response to a particular stimulus or situation by reinterpreting it in a less threatening way. However, there is growing evidence and appreciation that some types of emotion regulation are unintentional or incidental, meaning that affective modulation is a consequence but not an explicit goal. For example, affect labeling involves simply verbally labeling the emotional content of an external stimulus or ones own affective responses without an intentional goal of altering emotional responses, yet has been associated with reduced affective responses at the neural and experiential levels. Although both intentional and incidental emotional regulation strategies have been associated with diminished limbic responses and self-reported distress, little previous research has directly compared their underlying neural mechanisms. In this study, we examined the extent to which incidental and intentional emotion regulation, namely, affect labeling and reappraisal, produced common and divergent neural and self-report responses to aversive images relative to an observe-only control condition in a sample of healthy older adults (N = 39). Affect labeling and reappraisal produced common activations in several prefrontal regulatory regions, with affect labeling producing stronger responses in direct comparisons. Affect labeling and reappraisal were also associated with similar decreases in amygdala activity. Finally, affect labeling and reappraisal were associated with correlated reductions in self-reported distress. Together these results point to common neurocognitive mechanisms involved in affect labeling and reappraisal, supporting the idea that intentional and incidental emotion regulation may utilize overlapping neural processes.

Attentional bias and emotional reactivity as predictors and moderators of behavioral treatment for social phobia

Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety disorders, and evidence is accruing for the effectiveness of acceptance and commitment therapy (ACT). Little is known about factors that relate to treatment outcome overall (predictors), or who will thrive in each treatment (moderators). The goal of the current project was to test attentional bias and negative emotional reactivity as moderators and predictors of treatment outcome in a randomized controlled trial comparing CBT and ACT for social phobia. Forty-six patients received 12 sessions of CBT or ACT and were assessed for self-reported and clinician-rated symptoms at baseline, post treatment, 6, and 12 months. Attentional bias significantly moderated the relationship between treatment group and outcome with patients slow to disengage from threatening stimuli showing greater clinician-rated symptom reduction in CBT than in ACT. Negative emotional reactivity, but not positive emotional reactivity, was a significant overall predictor with patients high in negative emotional reactivity showing the greatest self-reported symptom reduction.

Cognitive Mediators of Treatment for Social Anxiety Disorder: Comparing Acceptance and Commitment Therapy and Cognitive-Behavioral Therapy

Objective To assess the relationship between session-by-session mediators and treatment outcomes in traditional cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for social anxiety disorder. Method Session-by-session changes in negative cognitions (a theorized mediator of CBT) and experiential avoidance (a theorized mediator of ACT) were assessed in 50 adult outpatients randomized to CBT (n = 25) or ACT (n = 25) for DSM-IV social anxiety disorder. Results Multilevel modeling analyses revealed significant nonlinear decreases in the proposed mediators in both treatments, with ACT showing steeper decline than CBT at the beginning of treatment and CBT showing steeper decline than ACT at the end of treatment. Curvature (or the nonlinear effect) of experiential avoidance during treatment significantly mediated posttreatment social anxiety symptoms and anhedonic depression in ACT, but not in CBT, with steeper decline of the Acceptance and Action Questionnaire at the beginning of treatment predicting fewer symptoms in ACT only. Curvature of negative cognitions during both treatments predicted outcome, with steeper decline of negative cognitions at the beginning of treatment predicting lower posttreatment social anxiety and depressive symptoms. Conclusions Rate of change in negative cognitions at the beginning of treatment is an important predictor of change across both ACT and CBT, whereas rate of change in experiential avoidance at the beginning of treatment is a mechanism specific to ACT.

Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry

Social anxiety disorder (SAD) is characterized at a neurobiological level by disrupted activity in emotion regulation neural circuitry. Previous work has demonstrated amygdala hyperreactivity and disrupted prefrontal responses to social cues in individuals with SAD (Kim et al., 2011). While exposure-based psychological treatments effectively reduce SAD symptoms, not all individuals respond to treatment. Better understanding of the neural mechanisms involved offers the potential to improve treatment efficacy. In this study, we investigated functional connectivity in emotion regulation neural circuitry in a randomized controlled treatment trial for SAD. Participants with SAD underwent fMRI scanning while performing an implicit emotion regulation task prior to treatment (n=62). Following 12 weeks of cognitive behavioral therapy, acceptance and commitment therapy, or wait-list, participants completed a second scan (n=42). Psychophysiological interaction analyses using amygdala seed regions demonstrated differences between SAD and healthy control participants (HC; n=16) in right amygdala-vmPFC connectivity. SAD participants demonstrated more negative amygdala-to-vmPFC connectivity, compared to HC participants, an effect that was correlated with SAD symptom severity. Post-treatment symptom reduction was correlated with altered amygdala-to-vm/vlPFC connectivity, independent of treatment type. Greater symptom reduction was associated with more negative amygdala-to-vm/vlPFC connectivity. These findings suggest that effective psychological treatment for SAD enhances amygdala-prefrontal functional connectivity.

Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder

Previous research has often highlighted hyperactivity in emotion regions to simple, static social threat cues in social anxiety disorder (SAD). Investigation of the neurobiology of SAD using more naturalistic paradigms can further reveal underlying mechanisms and how these relate to clinical outcomes. We used fMRI to investigate responses to novel dynamic rejection stimuli in individuals with SAD (N=70) and healthy controls (HC; N=17), and whether these responses predicted treatment outcomes following cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT). Both HC and SAD groups reported greater distress to rejection compared to neutral social stimuli. At the neural level, HCs exhibited greater activations in social pain/rejection regions, including dorsal anterior cingulate cortex and anterior insula, to rejection stimuli. The SAD group evidenced a different pattern, with no differences in these rejection regions and relatively greater activations in the amygdala and other regions to neutral stimuli. Greater responses in anterior cingulate cortex and the amygdala to rejection vs. neutral stimuli predicted better CBT outcomes. In contrast, enhanced activity in sensory-focused posterior insula predicted ACT responses.

Altered time course of amygdala activation during speech anticipation in social anxiety disorder.

BACKGROUND Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). METHOD Participants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Repeated measures multi-level modeling analyses were used to examine group differences in time course activity during speech vs. control anticipation for regions of interest, including bilateral amygdala, insula, ventral striatum, and dorsal anterior cingulate cortex. RESULTS The time course of amygdala activity was more prolonged and less variable throughout speech anticipation in SAD participants compared to HCs, whereas the overall magnitude of amygdala response did not differ between groups. Magnitude and time course of activity was largely similar between groups across other regions of interest. LIMITATIONS Analyses were restricted to regions of interest and task order was the same across participants due to the nature of deception instructions. CONCLUSIONS Sustained amygdala time course during anticipation may uniquely reflect heightened detection of threat or deficits in emotion regulation in socially anxious individuals. Findings highlight the importance of examining temporal dynamics of amygdala responding.