Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR): Design of a randomized controlled trial to increase positive affect in middle-aged and older adults with fibromyalgia.

BACKGROUND: Fibromyalgia syndrome (FMS) is a leading cause of functional limitations and disability for which there is no cure. Positive psychological interventions for improving health have received increasing attention, but evidence of the feasibility, acceptability, and impact of such interventions in adult populations with FMS is limited. OBJECTIVES: To describe the rationale and design of a 5-week, online positive affect skills intervention, LARKSPUR: Lessons in Affect Regulation to Keep Stress and Pain UndeR control. METHODS: FMS participants (N = 90) will be randomized to one of two conditions: (1) LARKSPUR or (2) emotion reporting/attention control. LARKSPUR is an online multicomponent intervention that targets eight skills to help foster positive affect: (1) noticing positive events, (2) savoring positive events, (3) identifying personal strengths, (4) behavioral activation to set and work toward attainable goals, (5) mindfulness, (6) positive reappraisal, (7) gratitude, and (8) acts of kindness. The primary outcomes include feasibility (i.e., recruitment, retention, adherence) and acceptability (i.e., helpfulness, usability, satisfaction). Secondary outcomes include pain intensity and pain interference. SIGNIFICANCE: If feasibility and acceptability metrics are met and reductions in pain outcomes are achieved, we will undertake future efficacy and effectiveness trials of LARKSPUR among older adults with FMS. TRIAL REGISTRATION: NCT04869345.

More than Hurt Feelings: The Wear and Tear of Day-to-Day Discrimination in Adults with Chronic Pain.

OBJECTIVE: To examine the extent to which self-reported experiences of discrimination are associated with pain interference among men and women with chronic non-cancer pain. METHODS: Data are from the Study of Midlife in the United States (MIDUS) Refresher Cohort. The analytic sample consisted of 207 adults with chronic pain (54.2 ± 12.8 years; 53.6% female) who completed the Major Experiences of Discrimination and Everyday Discrimination scales. Regression analyses examined cross-sectional relations between discrimination and pain interference. RESULTS: On average, the level of pain interference was moderate in the sample (mean = 3.46, standard deviation = 2.66; observed range 0-10). Approximately a third of respondents reported at least one major discriminatory event in their lifetime, while 22% reported three or more discriminatory lifetime events. Everyday discrimination scores averaged 14.19 ± 5.46 (observed range 0-33). With adjustment for sociodemographics, physical health, cognitive and psychological factors, social isolation, and loneliness, everyday discrimination was associated with increased pain interference (B = 0.099; 95% confidence interval [CI]: 0.02 to 0.17). CONCLUSION: These findings add weight to the importance of day-to-day experiences of interpersonal discrimination by documenting independent associations with functional interference in adults with chronic pain.

Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin.

Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized to pretreatment with oral rapamycin (6 mg) or placebo 2 h prior to the intravenous administration of ketamine 0.5 mg/kg in a double-blind cross-over design with treatment days separated by at least 2 weeks. Depression severity was assessed using Montgomery-Åsberg Depression Rating Scale (MADRS). Rapamycin pretreatment did not alter the antidepressant effects of ketamine at the 24-h timepoint. Over the subsequent 2-weeks, we found a significant treatment by time interaction (F(8,245) = 2.02, p = 0.04), suggesting a prolongation of the antidepressant effects of ketamine by rapamycin. Two weeks following ketamine administration, we found higher response (41%) and remission rates (29%) following rapamycin + ketamine compared to placebo + ketamine (13%, p = 0.04, and 7%, p = 0.003, respectively). In summary, single dose rapamycin pretreatment failed to block the antidepressant effects of ketamine, but it prolonged ketamine's antidepressant effects. This observation raises questions about the role of systemic vs. local blockade of mTORC1 in the antidepressant effects of ketamine, provides preliminary evidence that rapamycin may extend the benefits of ketamine, and thereby potentially sheds light on mechanisms that contribute to depression relapse after ketamine administration.

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

BACKGROUND: Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph-based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls. METHODS: 102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS: In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr during symptom provocation, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudal-ventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION: In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.

Associations between spouses' oxytocin receptor gene polymorphism, attachment security, and marital satisfaction.

OXTR rs53576, a polymorphism on the oxytocin receptor gene, has previously been linked to individual differences in social behaviors. That is, individuals with the GG genotype show greater empathy, sociability, and emotional stability. In the context of close relationships, such psychological resources are associated with better relationship outcomes. However, no studies to our knowledge have examined associations between spouses' OXTR polymorphisms, attachment security, and marital satisfaction. In the current study, 178 married couples (N = 356; ages 37-90) completed self-report measures of attachment security and marital satisfaction and provided saliva samples for genotyping. Results from Actor Partner Interdependence Models showed that individuals who had the GG genotype (actor effect) or had a spouse with the GG genotype (partner effect) reported greater marital satisfaction than individuals with AA or AG genotypes. Furthermore, greater attachment security mediated associations between GG genotype and marital satisfaction.