Effects of a Wellbeing Intervention on Inflammation Through Reward and Threat Processes

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.

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