Sleep and Healthy Aging Research for Depression (SHARE-D) Study

The Depressed Mood Subscale of the POMS is a self-and observer rated assessment of depressed mood in which severity of depressed mood is rated using a visual analog scale from 1 to 5 (5 being most severe). Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour

Depressed mood and depressive symptom severity by self-reported assessment using the Montgomery Asberg Depression Rating scale with a range from 0 to 54 with a higher score indicating more severe depressive symptoms. Each timepoint is scored and analyses examine the temporal profile of change with assessment every 2 hours

The Hamilton Depression Rating Scale is on the most widely used scales in depression, which is adapted to evaluate acute changes in depressive symptoms. A trained interviewer, blind to the experimental condition, make ratings of items of depressed mood, feelings of guilt, loss of interest, retardation/agitation, anxiety, and somatic symptoms using items from the Hamilton Depression Rating Scale. The 17-item version will be used.

This is a computer-based test that includes color photographs of facial expression of evoked-or felt-emotions: happy, sad, angry, fearful, disgusted, and nonemotional or neutral. Participants rate the emotional valence using a scale of 0-8 of each expression.

This is a computer-based test used along with emotion facial recognition to test subjective ratings of perceived intensity in response to facially-expressed emotions

This is a probabilistic reward task that is administered using computerized reward-learning task rooted in signal detection theory that yields an objective measurement of participant's ability to modulate behavior as a function of rewards. The variable that will be scored is termed response bias (RB), which reflects participants' preference for the stimulus paired with more frequent rewards.

Similar to the Reward Learning Task, this is a computer based reward task to evaluate reward processing in the context of monetary reward.

This will evaluate another component of reward by subjective reports and task sensitivity to general social rewards

The Snaith-Hamilton Pleasure Scale (SHAPS) is a self-administered questionnaire with 14 items assessing four domains of pleasure response/hedonic experience: interest/pastimes, social interaction, sensory experience, and food/drink, with each item scored from 1 to 4.

This self-report scale rates interest in 10 different activities, how much a person is interested in doing that activity right now

Using the Feelings of Social Disconnection Scale, participant rated the extent to which they were feeling the ''following feelings right now" on a 5-point Likert scale (1-not at all, to 5- very much so): (1) ''I feel like being around other people," (2) ''I feel like being alone," (3) ''I feel overly sensitive around others (e.g., my feelings are easily hurt)," (4) ''I feel connected to others," and (5) ''I feel disconnected from others." Items 1 and 4 were reverse-coded, and scores were averaged at each time point to create a measure of self-reported social disconnection. Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour

Physical "sickness" symptoms which have been related to the administration of endotoxin are assessed during the experimental protocol; these sickness symptoms include self-reported rating of severity of muscle pain, shivering, nausea, breathing, difficulties, and fatigue

The Brief Symptom Inventory will be used assesses a wide variety of psychiatric symptoms

Systemic inflammation as measured by circulating levels of interleukin-6 in plasma in pg/ml. Each timepoint is assayed and analyses examine the temporal profile of change with assessment every hour

Transcriptional profile of inflammation as measured by Conserved Translational Response to Adversity in circulating peripheral blood mononuclear cells

UCLA Loneliness scale is a 10-item scale designed to measure one's subjective feelings of loneliness as well as feelings of social isolation. Participants rate each item as either O ("I often feel this way"), S ("I sometimes feel this way"), R ("I rarely feel this way"), N ("I never feel this way").

MacArthur Scale of Subjective Social Status (i.e., Social Ladder) will be used to evaluate perceived social status

Social Support Questionnaire Scale will be used to evaluated perceived social support

The Attachment Style Questions will be used to evaluate feelings of social attachment. This scale is reported 18 items that rates how you feel generally experience in relationships, not just in what is happening in a current relationship.

Sensitivity to social rejection is examined by Fear of Negative Evaluation Scale and Mehrabian Rejection Sensitivity Scale

The Cyberball Social Exclusion Task is a virtual ball-toss game in which a participant plays with two other players (virtual) on a computer. Abruptly, the others exclude the participant, only throwing to one another. After completion of the task, the degree of perceived ostracism was was evaluated by a 20-item ostracism distress or social exclusion scale.

Increasing evidence indicates that inflammatory challenge acutely alters measures of cognitive performance, including spatial learning and memory. We use a virtual Morris Water Maze task (REF: https://pubmed.ncbi.nlm.nih.gov/19121374/) to assess computerized spatial learning and memory, followed by a Room Reconstruction Task (REF: https://pubmed.ncbi.nlm.nih.gov/10779831/) to assess the ability of cognitive mapping under real-life conditions.

Temporal summation reflects the endogenous capacity to enhance pain and will be assessed by calculating the windup ratio as a primary outcome for SHARE-Pain (or SHARE-P). Higher values are indicative of greater pain facilitation. Multiple pinprick probes were used (#3, #5, #6, and #7). The windup ratio will be calculated and z-scored within each probe. The z-scored windup ratios will then be averaged across probes to create an aggregate temporal summation index. Change scores will also be used to calculate temporal summation by subtracting the peak pain rating during 10 successive pinpricks from the pain rating during a single pinprick. The change scores will also be z-scored and averaged across probes. The windup ratio will be a primary outcome, whereas the change score metric will be a secondary outcome for SHARE-P.

Conditioned pain modulation assesses the degree to which one noxious stimulus reduces pain produced by a second noxious stimulus and is a measure of endogenous capacity for pain inhibition. It is calculated by taking the percent change in pressure pain threshold during the cold pressor task compared to the pressure pain threshold assessed just prior to cold water submersion. Larger values indicate better pain inhibitory capacity. This variable is a primary outcome for the SHARE-P. Raw difference scores will also be reported as a secondary outcome.

Affective pain modulation refers to the ability of negative emotions to enhance pain while positive emotions reduce pain. Participants will be asked to rate their pain on a 0 (no sensation) to 100 (intolerable) scale to two thermal stimuli (46°C and 48°C) presented in a randomized order throughout each condition.Self-reported pain will be compared across the three conditions (negative, positive, neutral). Affective pain modulation is a primary outcome for SHARE-

Pressure pain threshold is the pressure that first elicits pain, such that lower values indicate greater pain sensitivity. Pressure pain threshold was assessed at three sites: trapezius, masseter, and middle insertion of the quadriceps. Four trials were completed at each site (two on the left side two on the right side). All threholds will be z-scored within each site and averaged across sites to create an index score. Pressure pain threshold is a secondary outcome for SHARE-P.

The first thermal stimulus that participants self-report as painful (averaged across two trials). Lower values indicate enhanced pain sensitivity. This is a secondary outcome variable for the SHARE-P sub-study.

The thermal stimulus at which the participant identifies the pain as intolerable (averaged across two trials). Lower values represent greater pain sensitivity. This is a secondary outcome variable for the SHARE-P sub-study.

Cold pain tolerance is measured as the time it takes for the participant to withdraw their hand from cold water bath (2°C), such that shorter durations reflect greater pain sensitivity. (Secondary outcome for SHARE-P).

• Pressure pain threshold is the first mechanical stimulus that a participant self-reports as painful, such that lower values indicate greater pain sensitivity. Pressure pain threshold is the average of two readings and will be reported separately for the masseter muscle and middle of the quadriceps. These are tertiary outcomes for SHARE-P.

Pain intensity ratings will be assessed daily using a Visual Analogue Scale and averaged across the two week period to determine the Pain Intensity Index. These ratings will be made at baseline, 3mo, 6mo, 9mo, and 12mo and are considered a primary outcome for the longitudinal component of SHARE-P.

Depressive symptoms will be assessed at baseline, 3mo, 6mo, 9mo, and 12mo using the Patient Health Questionnaire - 9 item (PHQ-9). This is a primary outcome for the longitudinal component of SHARE-P.

Pain intensity and pain-related disability are assessed at baseline, 3mo, 6mo, 9mo, and 12mo using the Graded Chronic Pain Scale (3-month version). This is a secondary outcome for the SHARE-P study.

o Affective disturbance is assessed daily during a 2-week period by having participants rate the extent to which they feel three positive (happy, calm, agreeable) and three negative emotions (sad, anxious, annoyed) on a 0 (not at all) to 100 (extremely) scale. Daily positive affect and negative affect are calculated by averaging across the three positive and negative emotion words, respectively. Participants complete these measures at baseline, 3mo, 6mo, 9mo and 12mo. This is a secondary outcome for SHARE-P.

Electronic sleep diaries will be administered daily for two weeks at baseline, 3mo, 6mo, 9mo, and 12mo. Sleep diaries will be used to assess sleep continuity, including (1) latency to initial sleep onset, (2) frequency of nightly awakenings, (3) wake after sleep onset, (4) total sleep time, and (5) sleep efficiency (total sleep time/time in bed). These are considered secondary outcomes for SHARE-P.

Participants will receive an ActiGraph (wrist triaxial accelerometer) to wear for a 2-week period at baseline, 3mo, 6mo, 9mo, and 12mo to measure total sleep time (secondary outcome for SHARE-P).