Neural Mechanisms of Enhancing Emotion Regulation in Bereaved Spouses

Not Applicable

Completed

Conditions: Bereavement
Emotions
Depressive Symptoms
Grief
Affect

Registration Number: NCT04822194

Lead Sponsor: Bryan Denny

Brief Summary: This study investigates the underlying mechanisms of a novel emotion regulation intervention among recently bereaved spouses. More specifically, this study examines how thinking about an emotional stimulus in a more adaptive way can affect the relationship between psychological stress, psychophysiological biomarkers of adaptive cardiac response, and brain activity. The emotion regulation strategy targeted is reappraisal, specifically reappraisal-by-distancing (i.e., thinking about a negative situation in a more objective, impartial way) versus reappraisal-by-reinterpretation (i.e., thinking about a better outcome for a negative situation than what initially seemed apparent).

The study seeks to determine if relatively brief, focused reappraisal training in bereaved spouses will result in reduction of self-reported negative affect, increases in respiratory sinus arrhythmia (RSA; a measure of heart rate variability reflecting adaptive cardiac vagal tone), reduction in blood-based inflammatory biomarkers, and changes in neural activity over time. Reappraisal-by-distancing is expected to lead to greater changes in these variables relative to reappraisal-by-reinterpretation. Additionally, it is expected that across time decreases in self-reported negative affect, increases in RSA, reductions in blood-based inflammatory biomarker levels, and changes in neural activity will in turn lead to reductions in depressive symptoms and grief rumination. Finally, it is expected that distancing training will lead to reductions in depressive symptoms and grief rumination that are mediated by changes in the targeted neurobiological and behavioral mechanisms.

Detailed Description: The objective of this study is to use an experimental medicine approach to evaluate the basic psychological, psychophysiological, and neural mechanisms underlying a novel cognitive emotion regulation intervention aimed at improving psychological outcomes (e.g., reducing depressive symptoms and grief rumination) in recently bereaved spouses. Cognitive reappraisal (i.e. the ability to modify the trajectory of an emotional response by thinking about and appraising emotional information in an alternative, more adaptive way) represents a highly promising target for psychological intervention in bereavement. Reappraisal can be operationalized via two primary tactics: psychological distancing (i.e. appraising an emotional stimulus as an objective, impartial observer) and reinterpretation (i.e. imagining a better outcome than what initially seemed apparent). The current study builds upon promising preliminary work to investigate the effectiveness and underlying neurobiological mechanisms of a novel, five-session cognitive reappraisal intervention in bereaved spouses.

Recently bereaved participants (i.e. approximately 6 months post-spousal loss) will be randomly assigned to receive training in either distancing or reinterpretation, with five sessions occurring every 1-3 days, with longitudinal collection of affective, psychophysiological, physiological (i.e., blood draws to assess inflammatory biomarkers) and functional magnetic resonance imaging (fMRI) data. Follow-up questionnaire assessments will occur at one- and two-months post-intervention. The study aims to mechanistically relate changes in psychological, psychophysiological, physiological, and neural function during a novel emotion regulation intervention never before implemented in this stressed, high risk group. This research represents a Phase I, Stage I clinical trial. The primary endpoints are the assessments of the psychological, psychophysiological, physiological, and neural mechanisms mediating behavior change as a function of the cognitive emotion regulation intervention. The secondary endpoint is testing the efficacy of the intervention via assessment of psychological outcomes (i.e., the behavior change, as represented in changes in depressive symptoms, stress, and grief rumination).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

Inclusion Criteria

Recent loss of romantic partner within the past 5-7 months
At least 18 years of age
Minimum score of 25 on the Inventory for Complicated Grief
Must be able to speak, read, and write in English
Must be eligible to safely complete MRI scanning

Exclusion Criteria

Death of a second close family member/friend in the past year
Currently receiving psychotherapy
Diagnosed with obstructive pulmonary and/or heart disease, diabetes, liver failure, or kidney failure
Significant visual, auditory, or cognitive impairment
Divorced within the last year
Prior participation in a similar emotion regulation training protocol in Dr. Denny's lab
Any contraindication of MRI scanning (e.g., pregnancy, presence of any non-removable metal on or in the body, implanted medical devices, tattoos, medication patches, orthodontic braces or permanent retainers, hearing aids, history of claustrophobia or breathing disorders)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Self-reported Negative Affect	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks.	Self-reported negative affect data collected during the emotion regulation task on a 1-4 scale, with 1 meaning "not negative at all" and 4 meaning "very negative".
Respiratory Sinus Arrhythmia	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks.	Heart rate variability, or variability in time intervals between heart beats, as measured by the log of the root mean square of the successive RR interval differences (ln(RMSSD)). RR intervals are interbeat intervals between consecutive heartbeats. Average ranges for ln(RMSSD) for 30 to over 75 years of age range from 3.2 to 3.9 for women and 3.2 to 3.8 for men.
Neural Activity	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart.	Picture Induced Negative Emotion Signature (PINES) is an independently-defined, validated whole-brain neural pattern map for negative appraisal, with positive weights for areas like the amygdala and insula. PINES Correspondence Scores (PCS) are correlation coefficients derived for each trial type (Look Neutral, Look Negative, Reappraise Negative) per participant by correlating each participant's whole-brain pattern during the task to PINES. PCS correlation coefficients range from -1 to 1, and higher values reflect greater correlation to PINES and thus greater negative affect.
Grief Rumination	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.	Grief rumination assessed via Utrecht Grief Rumination Scale (UGRS) and the Inventory for Complicated Grief (ICG). UGRS items are rated from 1 (never) to 5 (very often). Scores range from 15 to 75; higher numbers represent higher grief rumination. These are summed from 3-item subscales Reactions, Injustice, Counterfactuals, Meaning, and Relationships, which all have score ranges of 3-15. Higher scores represent greater grief rumination. The ICG assesses grief via 19 first-person statements on a scale of 0 (Never) to 4 (Always) with a range from 0-76. Higher numbers reflect greater grief.
Depressive Symptoms	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.	Symptoms of depression assessed via the Center for Epidemiological Studies Depression (CES-D) scale, which asks participants to rate how often in the past week they have experience symptoms of depression, ranging from 0 (Rarely or none of the time) to 3 (Most of the time). Scores range from 0 to 60, with higher scores indicating higher levels of depressive symptoms.
Perceived Stress	Sessions 1 (baseline/initial session), 2, 3, 4, and 5, which were conducted approximately every 2-3 days over the course of 2 weeks, and at the 1- and 2- month follow-up.	Perceived stress assessed via the Perceived Stress Scale (PSS), consisting of 10 self-reported items asking participants how often they felt or thought a certain way, ranging from 0 (Never) to 4 (Very Often). Total range is 0 to 40, with higher scores indicate higher levels of perceived stress.

Secondary Outcome Measures

Name	Time	Method
Frequency of Reappraisal Usage	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.	Overall reappraisal usage frequency assessed via the Emotion Regulation Questionnaire Reappraisal facet score. Participants report using a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). Reappraisal facet scores may range from 6-42. Higher scores represent greater habitual reappraisal usage.
Physical Health	Sessions 1 (baseline/initial session) and 5, which were conducted approximately 2 weeks apart, and at the 1- and 2-month follow-ups.	Physical health and quality of life assessed via the RAND 36-Item Short Form Health Survey (SF-36) which assesses 8 subscales: physical functioning, social functioning, role limitations due to physical health problems, body pain, role limitations due to personal or emotional problems, emotional well-being, energy/fatigue, and general health perceptions. Each subscale ranges from 0 to 100, higher scores referring to more adaptive health outcomes.
Inflammatory Biomarkers	Sessions 0 and 6, which were conducted approximately 2-3 weeks apart.	Inflammatory biomarkers (e.g., serum IL-6, sIL-6R, IL-10, and TNF- α) measured via blood draw