Sleep and Healthy Aging Research on Depression for Younger Women

Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive attentional bias with an emotional dot probe task. Attentional bias is assessed by measuring reaction times to targets that appear in the same location as emotional (e.g., happy faces) versus neutral cues (e.g., neutral faces). Outcomes are change from baseline to post-injection in attentional bias towards positive vs neutral faces. Higher positive attentional bias scores indicate higher sensitivity to reward; negative attentional bias score indicate less sensitivity to reward. A score of 0 indicates no bias. The attentional bias score is derived by subtracting the reaction time in ms on congruent trials (dot replaces an emotional face) from the reaction time on incongruent trials (dot replaces the neutral face).

Time frame: Baseline and post-injection (2.7 hrs)

Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive emotion detection with a face morphing task. The outcome is the absolute change from baseline to post-injection in the percent of accurate responses. Higher accuracy is an indicator of higher sensitivity to reward and lower accuracy is an indicator of lower sensitivity to reward.

Time frame: Baseline and post-injection (2.8 hrs)

Motivation for general social reward is assessed via self-report; participants rate their desire to engage in 3 different activities, one of which is social, on a 1 (not at all) to 10 (extremely) Likert scale.; change in desire for the social activity from baseline to post-injection is the outcome variable. Higher values indicate higher motivation.

Time frame: Baseline and post-injection (2 hrs)

Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT) a behavioral computer task; change in the magnitude of response bias from baseline to post-injection is the outcome measure. More positive response bias indicates a bias towards the more frequently reward stimuli (a better outcome); more negative response bias indicates a bias towards the less frequently reward stimuli (a worse outcome). This is not a standardized scale with minimum and maximum values. Response bias is calculated using a formula from signal detection theory and is a logarithmic ratio derived from choice frequencies. The formula is log b=1/2log((Rich-correct+.5) \*(Lean-incorrect+.5)/(rich-incorrect+.5) \* (lean-incorrect+.5)), where rich refers to the more frequently rewarded option and lean refers to the less frequently rewarded option.

Time frame: Baseline and post-injection (2.25 hrs)

Population: For the Probabilistic Reward Task data are cleaned according to pre-specified quality controlled (QC) guidelines; data that do not meet these QC requirements are not included (e.g., participants who have accuracy less than 50%)

Motivation for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT), a behavioral computer task; change in the amount of hard trials chosen (relative to total trials) from baseline to post-injection is the outcome measure. The task is analyzed using generalized estimating equations (GEE) with a binary outcome; outcome values at each timepoint therefore range from 0 to 1, with higher numbers indicating higher motivation (a better outcome). The predictor for the GEE model is a time (coded as 0 and 1) by condition (coded as 0 and 1) interaction term. A negative result in the boxes below for each condition separately indicates a pre-to post-injection decrease in the proportion of hard trials chosen.

Time frame: Baseline and post-injection (2.1 hrs)

Sensitivity for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT) a behavioral computer task, tested as the strength of the association between increases in potential monetary reward for hard trials and selection of hard (vs) easy trials during the task. This is tested using generalized estimating equations, with condition (LPS vs. placebo) by time (pre vs post-injection) by reward magnitude (ranges from $1-$4.12) predicting hard (vs easy) trial choice. More positive values indicate higher reward sensitivity ( a better outcome), and lower values indicate lower reward sensitivity. The unit of measurement for the task is the proportion of hard trials chosen; the unit of measurement for the reward sensitivity outcome is a beta coefficient. For example, a positive coefficient for reward magnitude in the GEE output means that as the reward amount increases by one unit (e.g., $1), the odds of choosing the high-effort option increase.

Time frame: Baseline and post-injection (2.1 hrs)

Participants rate how much they are currently looking forward to different categories of rewarding activities on an analogue scale (0= not at all; 100=extremely); change from pre to post-experimental session is the outcome for anticipatory reward. Higher values indicate higher reward response.

Time frame: 14 days (7 days pre-injection; 7 days post-injection).

Participants spend 5 minutes talking about a close other to a research assistant trained in reflective listening and provide ratings of current negative and positive emotion on visual analogue scales (0=not at all; 100=extremely) using items from the Profile of Mood States. Outcome variables are change in self-report positive emotion from pre to post-discussion, and percentage of positive and negative emotional words used during the discussion (scored with Linguistic Inquiry and Word Count Software). Higher positive emotion and higher percentage of positive words indicates a greater social reward response.

Time frame: Post-injection (2.9 hrs)

Participants indicate the extent to which they enjoyed 10 activities (social, non-social, close social) on a 0-100 visual analogue scale (0= not at all; 100=extremely) at five random times during the day; change in enjoyment in each of the domains from pre to post-experimental session is the outcome for consummatory reward. Higher values indicate higher reward response.

Time frame: 14 days (7 days pre-injection; 7 days post-injection).

The Depressed Mood Subscale of the POMS is a self-reported assessment of depressed mood in which subjects rate severity of depressed mood using a visual analog scale from 1 to 10 (10 being most severe). Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour. The outcome reported below is the mean score at 2-hours post-injection, which is when the response to endotoxin is known to peak. Higher values indicate more depressive symptoms.

Time frame: Hourly, from pre-injection (T0) to 9 hours later (T9)

Count of eye blinks (resting eye blink rate; EBR) over a five minute period; the outcome is change in EBR from pre to post-injection. Higher values indicate higher dopaminergic activity.

Time frame: Baseline and post-injection (1.9 hrs)

Participants complete a 30 minute standardized emotion regulation task that includes two phases: a reactivity phase and a regulation phase, and assesses the ability to down-regulate negative emotional response to standardized images, using instructed reappraisal strategies. The dependent variable is the degree to which self-reported emotion changes when reacting to versus reappraising emotion stimuli. Participants rate how negative they feel on a 0 (not at all) to 100 (extremely) visual analogue scale before and after film clips. The change in negative emotion when reacting is compared to the change in negative emotion when regulating. More positive values indicate better emotion regulation.

Time frame: post-injection (approximately 3 hrs)