Clinical trial NCT06294145: Effects of a Wellbeing Intervention on Inflammation Through Reward and Threat Processes
Official title: Effects of a Wellbeing Intervention on Inflammation Through Reward and Threat Processes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Low Positive Affect
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2024-03-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All 20 participants will be assigned to the same 7-week savoring intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims to evaluate how savoring influences reward and threat processes and downstream inflammation. Savoring is designed to enhance positive affect, which may blunt stress responses and reduce downstream inflammation. The investigators aim to examine changes in the brain following the savoring intervention. The investigators are particularly interested in changes in brain activity that are correlated with changes in inflammation-related markers in the blood. In this single-armed pilot trial, the investigators will assess how savoring alters reactivity to rewarding and threatening experiences, and then examine related changes in downstream inflammation. The investigators intend to recruit 20 undergraduate students to complete a 7-week standardized savoring intervention. Participants will complete brain scans, daily diaries, questionnaires, a behavioral task, and blood collection at pre- and post-intervention assessments.

Detailed description: Interventions that enhance wellbeing have the power to improve both mental and physical health, but the exact mechanisms through which they confer these benefits remain unclear. Inflammation may be a key pathway; there is substantial evidence that both eudaimonic and hedonic wellbeing are associated with lower levels of inflammatory activity (Cole et al., 2015; Brouwers et al., 2013; Ironson et al., 2018), which may in turn have beneficial effects on health (Furman et al., 2019). However, wellbeing may influence inflammation through multiple mechanisms, including reward and threat processes (Dutcher et al., 2021; Eisenberger \& Cole, 2012). Identifying the mediating circuitry will help guide the development of targeted interventions able to protect against inflammation-related diseases, like depression. However, reward and threat processes have yet to be examined as potential mediators of wellbeing's effects on inflammation and health.

This study aims to evaluate how wellbeing may influence reward and threat processing and downstream inflammation using a novel savoring intervention (Positive Affect Treatment; PAT)(Craske et al., 2016; Craske et al., 2019). Savoring is a common component of many positive psychology and mindfulness interventions that involves cultivating sustained enjoyment of positive experiences. It is designed to enhance reward processing, which should in turn decrease threat processing and lead to blunted stress responses and reduced downstream inflammation (Eisenberger \& Cole, 2012). The investigators will collect daily diaries, neuroimaging, and questionnaires pre- and post-intervention to assess wellbeing, reactivity to social and nonsocial rewarding experiences, and buffering of stressful experiences in a single-armed pilot trial of 20 participants from the diverse undergraduate population at UCLA. The investigators will also collect blood samples to facilitate examination of immunological biomarkers.

By examining reward and threat processing at multiple levels inside and outside of the laboratory, the investigators aim to strengthen the understanding of how wellbeing alters the way humans perceive and interact with the world. Increased reward reactivity and decreased threat reactivity may be two key mechanisms through which wellbeing impacts stress physiology and downstream inflammation. The investigators will examine if the savoring intervention is associated with decreases in circulating inflammatory biomarkers, such as interleukin-6 (IL-6) and C-Reactive Protein (CRP), as well as reductions in pro-inflammatory gene expression. This study will also clarify whether savoring is an "active ingredient" driving the mental and physical benefits of many positive psychology and mindfulness interventions.

Eligibility criteria: Inclusion Criteria:

* Moderate to moderately severe depression indicated by a PHQ-8 score between 9 and 20
* Low positive affect indicated by a PANAS score of less than 24
* No anxiety to moderate anxiety indicated by a GAD-7 score of less than 15
* 18 to 25 years old
* English speaking
* Willing to refrain from starting other psychosocial/pharmacological treatments until study completion

Exclusion Criteria:

* MRI contraindications (left-handedness, claustrophobia, colorblindness, pregnancy, metal implants, and BMI above 35)
* Presence of disease that may influence inflammation (e.g. asthma requiring inhaler, autoimmune or inflammatory diseases, gum disease, sleep disorder, eating disorder)
* Presence of serious medical conditions (e.g. anemia, cancer (current or history), diabetes, endocrine disorder, fibromyalgia, heart problems)
* Presence of disease that may impact patterns of neural activity (e.g. Attention Deficit/Hyperactivity Disorder, bipolar disorder, schizophrenia, head trauma, epilepsy, problems with drugs or alcohol)
* Use of medications that may influence inflammation in last 6 months
* Bupropion, dopaminergic or neuroleptic medications in last 6 months, consistent with other studies that investigate anhedonia, given their potential influence upon reward processing
* Current use of heterocyclics and SSRIs if not stabilized for at least 3 months
* History of regular (5-7 times per week) drug use (marijuana, cocaine, stimulant use before age of 15)
* Current nicotine use (more than 11 cigarettes a week or nicotine equivalent)
* Prior or current behavioral activation psychotherapy
* Concurrent psychotherapy

Primary outcomes:
measure: Positive affect
timeFrame: Baseline and at 9 weeks
Secondary outcomes:
measure: Negative affect
timeFrame: Baseline and at 9 weeks
measure: Depression
timeFrame: Baseline and at 9 weeks
measure: Anxiety
timeFrame: Baseline and at 9 weeks
measure: Perceived stress
timeFrame: Baseline and at 9 weeks
measure: Psychological wellbeing
timeFrame: Baseline and at 9 weeks
measure: Emotions
timeFrame: Baseline and at 9 weeks
measure: Reward
timeFrame: Baseline and at 9 weeks
measure: Savoring strategies
timeFrame: Baseline and at 9 weeks
measure: Interoception
timeFrame: Baseline and at 9 weeks
measure: Inflammation
timeFrame: Baseline and at 9 weeks
measure: Sustained Attention
timeFrame: Baseline and at 9 weeks
measure: Neural Reward Activity
timeFrame: Baseline and at 9 weeks
measure: Neural Threat Activity
timeFrame: Baseline and at 9 weeks
measure: Daily diary
timeFrame: Baseline and at 9 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
References:
citation: Cole SW, Levine ME, Arevalo JM, Ma J, Weir DR, Crimmins EM. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology. 2015 Dec;62:11-7. doi: 10.1016/j.psyneuen.2015.07.001. Epub 2015 Jul 8.
citation: Brouwers C, Mommersteeg PM, Nyklicek I, Pelle AJ, Westerhuis BL, Szabo BM, Denollet J. Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure. Biol Psychol. 2013 Feb;92(2):220-6. doi: 10.1016/j.biopsycho.2012.10.002. Epub 2012 Oct 23.
citation: Ironson G, Banerjee N, Fitch C, Krause N. Positive emotional well-being, health Behaviors, and inflammation measured by C-Reactive protein. Soc Sci Med. 2018 Jan;197:235-243. doi: 10.1016/j.socscimed.2017.06.020. Epub 2017 Jul 10.
citation: Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019 Dec;25(12):1822-1832. doi: 10.1038/s41591-019-0675-0. Epub 2019 Dec 5.
citation: Dutcher JM, Boyle CC, Eisenberger NI, Cole SW, Bower JE. Neural responses to threat and reward and changes in inflammation following a mindfulness intervention. Psychoneuroendocrinology. 2021 Mar;125:105114. doi: 10.1016/j.psyneuen.2020.105114. Epub 2020 Dec 16.
citation: Eisenberger NI, Cole SW. Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat Neurosci. 2012 Apr 15;15(5):669-74. doi: 10.1038/nn.3086.
citation: Craske MG, Meuret AE, Ritz T, Treanor M, Dour HJ. Treatment for Anhedonia: A Neuroscience Driven Approach. Depress Anxiety. 2016 Oct;33(10):927-938. doi: 10.1002/da.22490.
citation: Craske MG, Meuret AE, Ritz T, Treanor M, Dour H, Rosenfield D. Positive affect treatment for depression and anxiety: A randomized clinical trial for a core feature of anhedonia. J Consult Clin Psychol. 2019 May;87(5):457-471. doi: 10.1037/ccp0000396.