Stress-Induced Inflammation and Reward Processing
Phase: NA
Conditions: Stress, Psychological
Sponsor: University of California, Los Angeles

 
 
1
Stress, Inflammation, and Well-Being 
Study Protocol 
PI: Chloe C. Boyle, Ph.D.; PI: Julienne E. Bower, Ph.D. 
 
 
University of California, Los Angeles IRB #16-001537 
Study Expiration Date: 
6/06/2019 
Version Date: 1.31.19 
 
BACKGROUND AND PROTOCOL SUMMARY 
 
Summary 
 
In this study we propose to examine the association between psychosocial stress, the stress-induced 
inflammatory response, and reward processing in a female undergraduate sample. Specifically, we 
will 1) examine effects of an acute psychosocial stressor on reward processing; 2) evaluate the 
association between stress-related changes in inflammation and reward processing; and 3) test key 
vulnerability factors that may moderate the association between stress and reward. To achieve 
these goals, this study will recruit 60 female undergraduate students to test effects of stress on 
reward processing in a 3.5 hour laboratory session. Participants will be randomly assigned to either 
experience a laboratory stressor or a placebo control (Het et al., 2009), and will complete reward 
tasks 90 minutes post stress/placebo onset, at which point the peripheral inflammatory response to 
stress reaches its peak (Kuebler et al., 2015). The reward tasks are computerized behavioral tasks 
that assess three domains of reward processing: reward-learning, reward motivation, and reward 
sensitivity. Throughout the session, all participants will complete self-report measures of affect 
and provide blood and saliva samples for evaluation of the psychological and physiological stress 
response. Within one week prior to the session, participants will attend a 1 hour visit in which they 
complete baseline reward tasks and self-report questionnaires assessing mood, personality, early 
life stress, and health behaviors. In total, participants will complete two visits, with a duration of 
4.5 hours. This study builds upon prior studies demonstrating immediate effects of acute stress on 
reward processing, and further tests for delayed effects of acute stress on reward processing. 
Furthermore, this will be the first study to examine inflammation as a mechanism linking stress to 
deficits in reward processing. Findings may inform theory of depression etiology and contribute 
to more specialized treatment that is targeted at specific symptoms of depression. 
 
1. Introduction and rationale 
 
Major depressive disorder (MDD) is debilitating, chronic, and widespread, with a lifetime prevalence of 16.2% 
for United States adults (Kessler, Merikangas, & Wang, 2007). The etiology and best treatment for MDD 
remains poorly understood, likely because clinical presentation of MDD is enormously heterogeneous. As such, 
research in psychopathology has begun to shift towards a dimensional approach in the study of mental illness, 
with a focus on fundamental psychological and biological processes rather than diagnostic categories (Insel et 
al., 2010; Miller & Rockstroh, 2013). One dimension receiving increasing attention is reward processing, 
impairments of which are associated with anhedonia. Most commonly defined in research as "an inability or 
reduced ability to experience pleasure", anhedonia actually reflects a broad array of potential deficits in reward-
related processes, including the ability to learn from, respond to, and motivate oneself towards reinforcing 
stimuli.  
 
Anhedonia is of particular interest in depression research for several reasons. In addition to its role as a key 
diagnostic symptom, there is evidence that anhedonia precedes the onset of depression and persists after 

 
 
2
depressive episode remission, suggesting that anhedonia may be a trait vulnerability contributing to onset and/or 
recurrence of depression (Hasler et al., 2004; Pizzagalli, 2014). For example, reward-related learning, measured 
as a tendency to develop a response bias towards rewarding stimuli, shows heritability and stability over time, 
and remains impaired in individuals currently in remission from MDD (Goldstein & Klein, 2014). Similarly, 
non-symptomatic healthy individuals higher in self-reported anhedonia exhibit subclinical neural and behavioral 
symptoms of depression, such as decreased neural reactivity in response to pleasurable stimuli in the ventral 
striatum, a brain region associated with reward functioning (Keedwell, Andrew, Williams, Brammer, & 
Phillips, 2005). 
 
Recent work has proposed a central role for stress in the relationship between reward processing and 
depression. Specifically, the induction of anhedonia through stress has been theorized to precipitate depression 
(Pizzagalli, 2014). Strong evidence in animal models, and preliminary evidence in human models, indicates that 
chronic and acute stress alters reward processing (Gold, 2015). In human studies, individuals with higher 
perceived stress and depressive symptoms show blunted reward-learning (Treadway et al., 2013; Pizzagalli et 
al., 2007), and experimental work has shown that acute stress blunts reward-related learning to a similar degree 
in healthy individuals (Bogdan & Pizzagalli, 2006). However, mechanisms linking stress, reward, and 
depression have not been determined.        
 
Converging evidence suggests that stress-related alterations in inflammatory biology may be a key mechanism. 
There is a substantial literature linking elevated inflammation to symptoms of depression, such as fatigue, social 
withdrawal, and anhedonia (Dantzer, O’Connor, Freund, Johnson, & Kelley, 2008; Eisenberger et al., 2010; 
Slavich & Irwin, 2014), including studies that demonstrate that inflammation experimentally elicited through 
typhoid vaccine can induce alterations in reward-learning (Harrison et al., 2015). Indeed, inflammation has been 
theorized to be a central pathway by which stress is transduced into depressive symptomatology (Slavich & 
Irwin, 2014). In animal models, inflammation has been shown to mediate the link between stress and anhedonic 
symptoms (Koo & Duman, 2008), but no studies have tested whether stress-induced inflammation influences 
reward processing in humans. 
 
Thus, the purpose of this study is to integrate findings from two key bodies of literature that have yet to be 
bridged: one suggesting that stress-induced anhedonia precipitates depression (Pizzagalli, 2014) and one 
suggesting that psychosocial stress-induced inflammation contributes to depression (Slavich & Irwin, 2014), by 
examining the effects of an acute psychosocial stressor on reward processing and the possible role of 
inflammation within these dynamics.  
 
Acute stress will be manipulated using a common psychosocial stress paradigm, the Trier Social Stress Task 
(TSST; Kirschbaum, 1993). Multiple facets of reward processing will be assessed to examine whether stress 
and/or inflammation is particularly influential in any given domain of reward processing, including reward 
motivation, reward learning, and reward sensitivity. Results from this study will advance our understanding of 
depression etiology by helping to clarify the nature of the well-documented association between stress and 
depression, and contribute to more targeted and individualized treatment for a highly heterogeneous and 
devastating disorder. 
Specific Aims and Hypotheses 
 
Aim 1: To examine effects of stress-induced inflammation on three domains of reward processing: reward 
learning, reward motivation, reward sensitivity. We hypothesize that increases in IL-6 following acute stress 
will predict decreased reward learning, motivation and sensitivity 90-120 minutes post stress.  
 
Aim 2: To test key vulnerability factors that may moderate the association between stress-induced inflammation 
and reward. We hypothesize that individuals with a) a history of early adversity, b) current depressive 

 
 
3
symptoms, or c) high trait anhedonia will evidence greater decrements in each of the three indices of reward 
processing in association with the stress-induced inflammatory response. 
 
Aim 3: To test whether the degree of reward dysregulation in response to stress-induced inflammation will 
predict increases in depressive symptoms and perceived stress, and decreases in positive affect, four months 
following the experimental session.  
 
2. Summary of Research Protocols 
 
Participants.  Participants will be biologically female, age 18-28 and fluent in English. Most will be UCLA 
undergraduate students recruited through the UCLA SONA system, although we will expand recruitment to the 
greater UCLA campus and surrounding neighborhood if necessary. A female sample will be recruited because 
stress effects on reward processing differ by gender (Lighthall et al., 2012), depressive symptoms and 
inflammation-related disorders are more prevalent among women (Slavich & Irwin, 2014) and previous work 
has shown correlations between the inflammatory response to endotoxin in females but not males (Moieni et al., 
2015). In addition, we will recruit 10 male UCLA undergraduate students for comparison purposes if funding 
permits. Compensation will be credit through the UCLA SONA system, or $50 for those not participating 
through SONA. Those who complete a 4-month follow-up survey will receive money derived from their 
performance on three of the reward processing tasks. 
 
Summary of Procedures. Study participation involves two visits. Visit 1 requires participants to come to the 
Mind-Body Laboratory for 1 hour. At this time we will obtain informed consent, and the participant will 
complete questionnaires and reward tasks. Visit 2 will be one laboratory visit that will last 3.5 hours. For Visit 
2, participants will be scheduled for an afternoon session to account for diurnal rhythms of cortisol. A research 
assistant will meet the participant at the Mind-Body Laboratory and walk them down to the Clinical and 
Translational Research Center (CTRC) at UCLA. Upon arrival, a nurse will take vitals and insert an intravenous 
catheter in the antecubital vein of the non-dominant arm for blood draws. Participants will complete 
questionnaires and computerized behavioral reward tasks, and then undergo an acute 15 minute laboratory 
psychosocial stressor, the Trier Social Stress Task (TSST), or a placebo control. They will then watch an 
emotionally neutral documentary video until 90 minutes post-stress onset, at which point participants will again 
complete behavioral reward tasks. Throughout the session, participants will provide saliva samples for analysis 
of cortisol reactivity and recovery (9 times), blood samples for analysis of immune activation (4 times), and 
self-report measures of affect for analysis of the psychological stress response (seven times). Blood pressure 
and heart will be assessed along with each cortisol assessment. At 200 minutes post-arrival, participants will be 
debriefed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
4
STUDY PROTOCOL 
 
1. Subject recruitment, protocol assignment, and eligibility evaluation 
 
1.1 Recruitment of participants  
 
Participants will be undergraduate students recruited through the UCLA SONA system and compensated for 
their participation with 5 hours’ worth of course credit. Participants will be told the experiment involves a 3.5 
hour session that includes providing blood and saliva samples, assessment of blood pressure and heart rate, 
completion of behavioral tasks, a challenge task, and self-report questionnaires, and an additional 1 hour session 
that includes completing behavioral tasks and self-report questionnaires. Interested participants will be asked to 
contact the study team through a study email and then screened by phone for eligibility. Participants will also be 
recruited through flyers posted on the UCLA campus and surrounding neighborhood; we will recruit 
participants who are between the ages of 18-28, biologically female and fluent in English to match the 
anticipated demographics of the SONA participants. In a brief phone interview, the PI or authorized study 
personnel will describe the purpose of the study and level of commitment involved.  
 
1.2 Participant inclusion and exclusion criteria 
 
Inclusion criteria. Participants will be biologically female, age 18-28 and fluent in English. Given that stress 
effects on reward processing differ by gender (Lighthall et al., 2012), that depressive symptoms and 
inflammation related disorders are more prevalent among women (Slavich & Irwin, 2014) and that previous 
work has shown correlations between inflammatory markers and psychological response to endotoxin in 
females but not males (Moieni et al., 2015), we will restrict recruitment to a female sample. We aim to recruit 
an additional 10 male participants for comparison purposes if additional funding is obtained. 
 
Exclusion criteria. Participants will be excluded for the presence of disorders with an inflammatory 
component, such as colitis, rheumatoid arthritis, asthma, and untreated allergies, as well as regular use of steroid 
medications known to influence neuroendocrine or inflammatory systems. Participants with recent or acute 
illness will be eligible but scheduled to participate after at least two weeks without illness. Participants who 
smoke or meet criteria for alcohol use disorder will be excluded. Women currently or imminently planning to 
become pregnant will not be eligible.  
 
1.3 Phone Screening Evaluation   
 
Individuals interested in participating will be asked to contact the research staff through a study email and then 
screened for eligibility. In a 10-15 minute phone interview, the PI/research team will describe the study and 
level of commitment involved. If the individual is still interested, the participant will be screened for 
inclusion/exclusion criteria. The PI will then review the screening to determine if screening for alcohol use 
disorder is warranted. If the participant meets criteria for alcohol use disorder, the PI will refer the participant to 
campus resources for treatment (UCLA Counseling and Psychological Services). If the participant is eligible, 
the PI will randomly assign the participant to the stress or placebo control condition using a random number 
generator. Participants will then complete Visit 1. For Visit 2, participants will be asked to refrain from drinking 
(water ok) and eating for one hour prior due to potential effects on inflammatory and HPA axis activity. 
 
2. Laboratory Protocol 
 
2.1 Informed Consent 
 

 
 
5
During Visit 1, participants will complete the consent process. Consent will be conducted by the study PI or 
authorized study personnel. Consent procedures will take place at the Mind-Body Laboratory in a private room. 
The participant will be offered as much time as necessary to review the permission form and to ask questions 
before providing a signature indicating agreement to participate in the study.  
 
Overview of Laboratory Session 
Participants will be scheduled for Visit 1 at the Mind-Body Laboratory. Visit 1 will last 1 hour. Upon 
completion of the consent procedures, the participant will complete behavioral reward tasks and questionnaires 
and then scheduled for Visit 2. Visit 2 will be scheduled in the afternoon. Participants will be instructed to meet 
the research team at the Mind-Body Laboratory; a research assistant will then walk the participant down to the 
Clinical and Translational Research Center (CTRC) at UCLA. Upon arrival, a nurse will insert an intravenous 
catheter in the antecubital vein of the non-dominant arm for blood draws. The maximum amount of blood to be 
drawn from each participant is 90 mL, or 6 tablespoons. This is a routine medical procedure. Participants will 
then complete baseline questionnaires assessing recent behaviors that might influence the physiological stress 
response (e.g., sufficient sleep the previous night). At pre-specified intervals, participants will complete 
measures of state affect, self-conscious emotions, and task appraisals. Participants will then complete three 
behavioral reward tasks, the probabilistic reward task (PRT; 14-15 minutes) the dot probe task (5-6 minutes), 
and an emotion identification task (5 minutes). Participants will provide their saliva and blood samples at 
specific intervals (see 2.6 section below). They will next receive instructions for the Trier Social Stress Task 
(TSST) or for the Placebo-TSST (P-TSST). After the TSST/P-TSST, participants will watch a 60-minute 
emotionally neutral documentary. At 90 minutes post TSST/P-TSST onset, participants will complete the PRT, 
dot probe and emotion identification task for a second time (counterbalanced), an effort expenditure task for the 
first time (15 minutes), and a charitable giving task (administered last, 3 minutes). Administration of the tasks 
will take approximately 50 minutes. At 200 minutes post-arrival, participants will be debriefed.  
 
2.2 Behavioral Reward Tasks 
 
2.2a Reward-related learning. The Probabilistic Reward Task (PRT) (Pizzagalli et al., 2005) is a 14-15 minute 
signal-detection task that objectively measures reward-related learning. The PRT uses an asymmetric 
reinforcement schedule with social reward (positive feedback). In each trial, participants identify which of two 
difficult-to-differentiate stimuli are presented. The stimuli are cartoon faces with one of two straight mouths 
(10mm short mouth versus 11mm long mouth). At the beginning of a trial, the face has no mouth, and then one 
of the faces with the mouth is briefly presented. Participants are asked to indicate which of the two faces was 
presented. Unbeknownst to the participant, an asymmetrical reinforcement schedule is used to induce a response 
bias towards one of the faces (termed the "rich" stimulus), with one of the faces rewarded three times more 
frequently than the other (termed the "lean" stimulus). Both faces are presented an equal number of times. In 
healthy individuals, this reinforcement schedule leads to an implicit response bias favoring the more frequently 
rewarded stimulus; the magnitude of this response bias is used to operationalize reward learning and is used as 
the dependent variable in the proposed study. 
 
The task consists of a total of 200 trials divided in two blocks. Each block lasts 7 minutes, and 
participants have a 30 second break in between blocks. Each trial begins with the presentation of a fixation 
cross in the middle of the screen [750 ms], followed by the presentation of a mouthless cartoon face [500ms] 
and then presentation of a face with a mouth [100 ms]. The mouthless face remains on the screen as the 
participant uses the keyboard to indicate whether the short or long mouth was presented. For each block, 40 
correct response trials are followed by positive feedback [1500ms] ("Correct! You won 5 cents!"). If the 
participant is inaccurate, or accurate on a non-rewarded trial, a blank screen is displayed [1750ms]. Participants 
are informed that only some correct responses will be rewarded prior to the task. Because the PRT will be 
administered before and after the TSST/P-TSST, one administration will use mouth size stimuli, and one 
administration will use nose size stimuli, in order to reduce practice effects. 
 

 
 
6
Example of PRT mouth stimuli 
 
 
 
 
 
 
 
 
 
 
2.2b Reward Motivation. The Effort Expenditure for Rewards Task (EEfRT; Treadway & Zald, 2011) 
operationalizes reduced motivation for a reward as a decreased willingness to exert greater effort for higher 
rewards, particularly when rewards are uncertain. In the task, participants are presented with a series of trials in 
which they choose between a “hard-task” and an “easy task” in order to earn varying amounts of money. They 
win money by pressing a button a predetermined amount of times within a set time frame. Hard-task trials 
require the subject to make 100 button presses using the non-dominant little finger within 21 seconds. The easy-
task requires 30 button presses using the dominant index finger in 7 seconds. Subjects can win $1.00 for easy-
task trials. For the hard-task, participants can win a varying amount with a range of $1.24 -$4.30 (varying 
reward magnitude). In addition, participants are told that only some of the trials will give them a reward for a 
correct response. They are given probability information on whether the trial is a possible win trial or not (88%, 
50%, 12%). Probability of reward and reward magnitude are manipulated to look at the conditions under which 
a person will exert effort for a reward. The EEfRT takes 15 minutes; participants have a 30 second break 
halfway through the task. Participants will be told they can win the summed amount of two randomly selected 
trials from the task. The amount a participant can win ranges from $2.00 to $8.24. The EEfRT will be 
administered at Visit 1 and after the TSST/P-TSST. 
 
2.2c Perceptual Reward Sensitivity. A 6 minute computer based dot probe task will be used to assess for 
attentional bias towards positive facial stimuli. Positive social stimuli, such as happy facial expressions, are 
conceptualized as primary rewards that elicit approach oriented behavior (Berridge & Kringelbach, 2008; Yoon 
et al., 2009). The response in healthy controls is increased bias towards happy versus neutral faces, which is 
indexed as faster reaction time when a visual probe replaces the happy face on either the right or left side of the 
screen. During the task, participants are informed that they will see a dot appear on either the right or left side of 
the computer screen, and that their task is to respond as quickly as possible by pressing one of two keys 
indicating the side the dot is on. Prior to seeing the dot participants are told they will see two faces (flashed 
side-by-side on screen for 500 ms to allow for conscious processing of the stimuli) but do not need to respond to 
them. They will view a total of 40 pairs of photographs of different faces, with each pair consisting of two 
photographs of the same person side-by-side on the screen. One photograph is of a neutral expression, while the 
second is emotional (angry, sad, happy, happy-low arousal). There are 10 pairs of neutral/angry, 10 pairs of 
neutral/sad, 10 pairs of neutral/happy-low arousal, and 10 pairs of neutral/happy faces. Each pair is presented 
four times so that all possible combinations of emotional face location (left, right) and dot location (left, right) 
are seen. There are a total of 160 trials (all face pairs are randomized for each participant). Angry and sad faces 
are included to assess whether any effects of stress or inflammation on attentional bias are specific to positive 
stimuli. All faces will be taken from the NimStim set of facial expressions (Tottenham et al., 2009), which is in 
color and has a diverse set of models for each expression. The dot probe task is completed before and after the 
TSST/P-TSST. 
 
2.2d.  Emotion identification task. In the emotion identification task, participants will be presented with a 
picture depicting different emotions at various levels of intensity. These pictures were created by morphing 
photographs that display different emotions (e.g., Sad, Angry) (Pollak & Kistler, 2002). Therefore, the 

 
 
7
photographs will vary in emotional intensity within a continuum that ranges from neutral to sad, neutral to 
happy, neutral to angry, or neutral to fearful. Twenty two pictures (11 males; 11 females) within each emotion 
pair (e.g., Neutral vs. Sad) will be presented at 10% increments of intensity of the target emotion (e.g., 0% sad, 
10% sad, … 100% sad). All faces will be taken from the NimStim set of facial expressions (Tottenham et al., 
2009). After the presentation of each picture, the participant will be asked to indicate which emotion the face 
resembled most by making a choice via a left or right button on a response box (e.g., NOTHING vs. SAD or 
NOTHING vs. HAPPY, etc).  This task will take approximately 5 minutes and is completed before and after the 
TSST/P-TSST. 
 
2.2e. Prosocial choice and emotional reactivity. This task will be administered at the end of Visit 2. Participants 
will complete a computer task that asks participants whether they would like to donate up to $10 of their 
potential earnings to a well known charity (e.g., American Red Cross) or a charity of their choice (Barraa, 
McCullough, Ahmadi, & Zak, 2011). After making their decision, participants will complete the VAS measures 
used throughout the session to assess affective reactivity to prosocial behavior. Participants are told this is an 
anonymous decision. Regardless of their choice, participants will receive their money if they respond to a 
subsequent questionnaire at the 4-month follow-up. The dependent variable is choice to donate (yes/no) and 
amount donated (continuous measure). This task will be included because charitable giving is associated with 
heightened reactivity in reward-related regions in the brain (Harbaugh, Mayr, & Burghart, 2007).  
 
2.2f. Prosocial behavior. The Dictator Game (DG) and the Ultimatum Game (UG; Guth, Schmittberger, & 
Schwarze, 1982) are brief computer tasks that will be used to measures pro social decision making. In the DG, 
the participant is given a role (Player B) and asked to allocate money that is presented in a decision tree format 
to another person (Player A) and herself.  The participant has the choice to allocate the money in a more or less 
prosocial manner (e.g., choosing an option in which both parties receive money even though the participant 
could otherwise receive more money). There are 6 trials. The UG is similar, but incorporates an element of risk. 
Across eight trials, the participant decides how to split the money with an opponent player. If the opponent 
rejects the offer, both parties lose the money. Fair offers are more likely to be accepted. The dependent variable 
is the average amount the participant proposes, with higher numbers indicating more prosocial behavior. Order 
of administration of the UG and DG will be counterbalanced. Total administration time is 5 minutes. The 
participant is told they can win up to $5 based on their performance on the games. These tasks will be 
administered at Visit 1 and are considered exploratory. We will test whether higher prosocial tendencies 
moderate the stress-induced inflammatory response.  
 
2.3 Trier Social Stress Task (TSST) and Placebo–TSST 
 
Following completion of pre-stress reward tasks, participants next receive instructions for the Trier Social 
Stress Task (TSST; Kirchbaum, 1993) or for the Placebo-TSST (P-TSST; Het et al., 2009). The TSST is a 
commonly used 15 minute psychosocial laboratory stressor, in which participants are asked to imagine that they 
are invited to an interview for a position they find desirable (e.g., research assistant position, internship) and are 
told that they will be delivering a five-minute speech on how they are an ideal candidate. Participants are 
informed that their performance will be recorded and evaluated. They are given three minutes to prepare their 
speech, and then deliver the speech for five minutes in front of a panel of two student research assistants who 
are trained to provide nonverbal negative feedback and are dressed in white laboratory coats. Participants then 
complete a five-minute mental arithmetic task in front of the panel in which they are asked to count backwards 
by 13 from 2,395 as quickly and as accurately as possible. They receive corrective feedback from the panel each 
time they make a mistake, and are asked to start over. The TSST reliably activates the HPA stress axis, 
influences immunological parameters, and leads to high levels of self-reported stress and anxiety (Frisch, 
Häusser, & Mojzisch, 2015; Steptoe et al., 2007). The P-TSST parallels the TSST in terms of general procedure 
and duration but removes social evaluative components and does not elicit a strong physiological response. In 
the P-TSST, participants prepare for three minutes to talk out loud about a neutral topic (e.g., describing a 

 
 
8
recent movie or book that they have read). While in a room alone, they speak out loud for five minutes, and then 
count forwards by 15s, starting at 0. The P-TSST was chosen for the proposed study because it provides some 
control for effects of cognitive load on performance in the behavioral reward tasks (Frisch et al., 2015). 
 
2.4 Neutral Movie 
 
Following the TSST/P-TSST, participants will watch a neutral documentary video. The neutral video will be 
episodes from “How It’s Made” from the Discovery Learning Channel, which describes how a number of 
everyday objects are manufactured, and was chosen to be both neutral and interesting. Participants watch this 
video for approximately 60-75 minutes. The video is stopped at 90 minutes post TSST/P-TSST onset, at which 
point behavioral reward tasks are administered. 
 
2.5 Self-report questionnaires during the laboratory session 
 
2.5a Emotional reactivity and recovery. Emotional reactivity and recovery from the TSST/P-TSST will be 
assessed using items from the Positive and Negative Affect Schedule (Watson & Clark, 1999; Thompson, 
2007), including the negative and positive affect scales (10 items each). Additional items from the serenity 
subscale will be used to assess low arousal positive affect and two items will be created for this study (apathetic, 
numb). Participants will rate how they feel “right now (that is, at the present moment) on a 1 (very slightly or 
not at all) to 5 (extremely) Likert scale. These questions will be administered seven times, upon arrival, prior to 
the stressor, immediately post stressor, and 60, 90, 120, and 150 minutes post stress onset. This will allow us to 
examine effects of stress on positive and negative affect, and to determine associations between performance on 
behavioral tasks and emotional responses. Additional emotions relevant to feelings of fatigue will also be 
assessed using items from the Profile of Mood States Scale-short form (Curran, Andrykowski, & Studts, 1995). 
Participants will complete the fatigue (8 items) vigor (5 items) and confusion subscales (7 items) alongside the 
PANAS. Participants will rate how they feel “right now (that is, at the present moment) on a 1 (very slightly or 
not at all) to 5 (extremely) Likert scale.  
 
Given previous work directly linking self-conscious negative emotions to the inflammatory response 
(Dickerson et al., 2009), participants will also complete the State Shame and Guilt Scale (Marschall, Sanftner, 
& Tangney, 1994) after the TSST/P-TSST. Example items include: “I want to sink into the floor and 
disappear”; “I feel humiliated, disgraced”; “I feel like I am a bad person” to measure guilt.  Participants rate 
how much each statement is accurate about how they feel at the current moment on a 5-point scale ranging from 
not feeling this way at all (1) to feeling this way very strongly (5). 
 
Given research showing that associations between subjective response to the TSST and stress 
physiology may be more detectable using visual analogue scales (VAS) during the stressor (Hellhammer & 
Schubert, 2012), participants will be asked to rate how stressed, anxious, angry, confident, calm, socially 
connected and happy they are currently feeling using a visual analogue scale alongside the PANAS and at the 
following additional time points: prior to speech instructions, after speech preparation, after the speech, and 
after the math portion of the TSST/P-TSST. Additionally, at the end of Visit 2 participants will complete a 
modified version of the Intrusive Thoughts subscale from the Impact of Events Scale (Horowitz, Wilner, & 
Alvarez, 1979) to assess the degree to which they ruminated about the TSST. 
 
2.5b Cognitive appraisal. The Primary and Secondary Appraisal Scale (Gaab, Rohleder, Nater, & Ehlert, 2005) 
will be used to assess how participants evaluate the stressor. Participants rate whether they agree with 
statements such as “I do not feel threatened by the situation,” “Whether the experts judge me positively mainly 
depends on me.” Participants complete this task prior to the TSST/P-TSST.  
 
2.5c Session evaluation. After each behavioral reward task, participants will be asked to answer questions 
assessing task appraisal (enjoyable, difficult, interesting; chosen to reflect emotions consistent with reward 
processing) on a 1 to 5 Likert scale. After completing the TSST/P-TSST, participants will complete 5 questions 

 
 
9
assessing task impressions (e.g., “The panel was harsh in their evaluations”) on a 1-7 scale, and 17 questions 
assessing post-task appraisals (e.g., “I did well on the tasks”) on a 1-7 scale. Prior to the debriefing, participants 
will be asked open-ended questions about their impressions of the laboratory session. 
 
2.6 Inflammatory and neuroendocrine response to acute stress 
 
2.6a Inflammation. Participants will provide their first blood draw 45 minutes after arriving to allow for 
reactivity to the novel situation to subside. Subsequent blood draws will be completed 60, 90, and 120 minutes 
post-stress onset.  Research suggests the peak of the inflammatory response following the TSST is 90 minutes 
post stress completion, with elevations still evident at 120 minutes (Kuebler et al., 2015). The 90-minute peak 
will be used in the proposed study to examine associations between inflammation and performance on 
behavioral reward tasks. All blood samples will be collected by venipuncture into ethylene diamine tetra-acetic 
acid tubes and placed on ice immediately after collection. At each of the four time points, collection will be for 
two 6 mL lavender tops for assessment of peripheral levels of IL-6 and one 2.5mL PAXgene tube for 
assessment of proinflammatory gene expression.  After the study session, nursing staff will take the samples to 
the Pathology Research Portal for processing and storage. Samples will be centrifuged for acquisition of plasma 
and stored at -80°C. At study completion, samples will be taken to the UCLA Inflammatory Biology Core 
Laboratory and assayed for IL-6 using a high sensitivity enzyme-linked immunosorbent assay (ELISA) (R&D 
Systems, Minneapolis, Minn). Samples will be assayed in duplicate and each subject’s samples will be assayed 
in the same run to avoid interassay variability. Plasma and RNA samples will be stored for future assays.   
 
2.6b Cortisol. Participants will provide nine saliva samples across the 3.5 hour session for assessment of 
cortisol reactivity and recovery. Saliva samples will be collected using Salivettes (Sarstedt, Inc) and stored at -
80°C. They will be shipped to the Kirschbaum lab in Germany where they will be assayed for cortisol in 
duplicate using an enzyme-linked immunoabsorbent assay. Samples will be collected upon arrival, after 
baseline reward tasks, immediately post stressor, and 15, 30, 45, 75, 105, and 135 minutes post stressor. Heart 
rate and blood pressure will also be monitored at each of these time points. 
 
2.7 Debrief 
 
At 200 minutes post-arrival, participants will be debriefed. Participants will first answer several questions 
assessing their impressions of the laboratory session. Research assistants will then use a script to debrief the 
participant, which informs the participant that the performance of the participant was not recorded and that no 
analysis of the participant’s speech or math performance will be conducted. Research assistants will explain that 
the tasks were unreasonably difficult and do not reflect upon the participant's aptitude or ability. The debriefing 
is modified for those who did not experience the TSST. All participants also receive a resource sheet for 
counseling services at UCLA.  
  
3. Questionnaires. 
 
Participants will be asked to complete questionnaires at Visit 1 through the online survey platform Qualtrics. 
Questionnaires will be administered before the experimental session to avoid carryover effects of the 
questionnaires on the behavioral tasks (and vice versa) during the session. Questionnaires will take 
approximately 30 minutes to complete. Participant will complete the questionnaires in a private room at the 
Mind-Body Laboratory.  
 
Questionnaires will assess demographics, health behavior (including exercise and sleep), personality, and 
mental health history. These measures will be used to characterize the sample. Questionnaires will also assess 
trait and state anhedonia, depressive symptoms, and early life adversity. These measures will be used to 
examine vulnerability factors that may moderate effects of stress on reward processing.   

 
 
10
 
3.1 Characterizing the sample 
 
3.1a Anxiety symptoms. The 7-item Generalized Anxiety Disorder-7 will be used to assess anxiety symptoms. 
Prior research has shown that heightened levels of anxiety are associated with reward processing under stress 
(Morris & Rottenberg, 2015). Participants are asked to indicate how often during the past two weeks they have 
felt bothered by symptoms such as feeling on edge, worrying, and having trouble relaxing on a 0 (not at all) to 3 
(nearly every day) scale. 
 
3.1b Personality. Two subscales from the 24 item Eysenck Personality Questionnaire-Revised short form 
(EPQR-S; Eysenck & Eysenck, 1992), assessing extraversion and neuroticism, will be used to assess 
personality. Extraversion is associated with mesolimbic dopaminergic reward processing and it has been 
proposed that extraverts are more sensitive to reward than introverts (Smillie, Wacker et al., 2015). Other work 
suggest that neuroticism is associated with reduced neural reward processing (Kehoe, Toomey, Balsters, & 
Bokde, 2012). We will also administer the LOT-R to assess optimism; this trait has been posited to be 
associated with reward processing and underlie resilience to stress (Southwick, Vythilingam, & Charney, 2005) 
 
3.1c Affect. Trait positive and negative affect will be assessed using items from the Positive and Negative Affect 
Schedule (Watson & Clark, 1999), including the negative and positive affect scales (10 items each) and 
additional items from the joviality, guilt, serenity and sadness subscales. Additional items specific to this study 
(apathetic, numb) will also be included. Participants will rate how often they generally feel each emotion on a 0 
(very slightly or not at all) to 4 (extremely) Likert scale. This questionnaire will also be administered through an 
online link for a follow-up assessment the academic quarter after the participant completes her session. 
 
3.2 Vulnerability factors that may moderate effects of stress on reward. 
 
3.2a Consummatory anhedonia. The Snaith Hamilton Pleasure Scale (Snaith et al., 1995) assesses the ability to 
experience pleasure in the last few days on a scale of 1(strongly disagree to 4 (strongly agree). Participants 
respond to statements such as “I would find pleasure in small things, e.g. bright sunny day, a telephone call 
from a friend.” 
 
3.2b Social anhedonia. The Chapman Social Anhedonia Scale Revised (CSASR; Mishlove & Chapman, 1985) 
is one of the most widely used measures of anhedonia and consists of 40 yes/no questions. It assesses pleasure 
experienced when interacting with others and interest in having close social connections (e.g., “A car ride is 
much more enjoyable if someone is with me.”) Higher scores indicate less ability to experience pleasure. The 
Multidimensional Personality Questionnaire-Brief Form – Social Closeness Scale (Patrick, Curtin, & Tellegen, 
2002) consists of 12 yes/no items. It will be used because the CSASR has been criticized for poor psychometric 
functioning (Olino et al., 2016) and cultural bias (Leventhal et al., 2006) and researchers have advocated its use 
for assessment of social anhedonia (Olino et al., 2016; Reise, Horan, & Blanchard, 2011). To control for 
potential confounding of social anhedonia with social phobia, the 3-item Mini-Social Phobia Inventory (MSPI; 
Connor, Kobak, Churchill, Katzelnick, & Davidson, 2001), will also be administered. The MSPI has shown 
sound psychometric properties, including strong sensitivity in treatment seeking samples (Weeks, Spokas, & 
Heimberg, 2006). To control for potential confounding of social anhedonia with lack of social support, will also 
examine perceptions of social support through the attachment subscale of the Social Provisions scale (Cutrona 
& Russel, 1987; 4 items). 
 
3.2c Physical anticipatory and physical consummatory anhedonia. The Temporal Experience of Pleasure Scale 
(Gard, Gard, Kring, & John, 2006) is an 18 item scale that assesses anticipatory and consummatory anhedonia 
in the physical realm. Participants rate how true each statement is for them in general on a 1 (very false for me) 

 
 
11
to 6 (very true for me) scale. Example items: “I really enjoy the feeling of a good yawn” and “When ordering 
something off the menu, I imagine how good it will taste.”   
 
3.2d Reward Sensitivity. Behavioral inhibition and behavioral activation scales (BIS/ BAS; Carver & White, 
1994). These scales are proposed to represent two basic motivational systems, an approach oriented appetitive 
system and an avoidance oriented inhibited system. This 24 item scale assesses individual differences in the 
sensitivity of each system. The BAS is composed of the following three subscales: drive, fun seeking, and 
reward responsiveness. Participants rate their agreement with statements like “I often act on the spur of the 
moment” on a 1 (very true for me) to 4 (very false for me) scale. 
 
3.2e State anhedonia. The Mood and Anxiety Symptom Questionnaire anhedonia subscale (Watson et al., 1995) 
is 14 items and assesses anhedonic symptoms over the past week. Participants indicate how often they have had 
“feelings, sensations, problems and experiences that people sometimes have” such as “Felt like I had a lot of 
interesting things to do” on a 5-point Likert scale (1 = not at all; 5 = extremely). This questionnaire will also be 
administered through an online link for a follow-up assessment the academic quarter after the participant 
completes her session. 
 
3.2f Early life stress. In the Risky Families Questionnaire (Repetti, Taylor, & Seeman, 2002), participants 
indicate the extent to which they lived in a home characterized by high conflict, low parental warmth, and a 
chaotic or unpredictable daily experience as a child.  Items are rated on a 1 (not at all) to 5 (very often) scale. 
The Adverse Childhood Experiences checklist (ACEs) (Chapman et al., 2004; Dube, Felitti, Dong, Giles, & 
Anda, 2003) is a 10-item checklist including: parent separation/divorce, domestic violence, family member in 
prison, maltreatment, and family member with mental illness or substance abuse. This scale has been used 
extensively in both psychology, psychiatry, pediatric, and epidemiological research, where exposure to more 
than 3 ACEs is associated with increased risk for both physical and mental illness (Chapman et al., 2004; 
Chapman, Dube, & Anda, 2007; Dube et al., 2003). 
 
3.2g Depressive symptoms. The 20-item Center for Epidemiologic Studies-Depression scale (Radloff, 1977) is a 
reliable and valid 20-item self-report scale developed for the general population to assess depressive 
symptomatology. Participants are asked to rate how often they have experienced depressed feelings, attitudes, 
and behavioral symptoms during the past week (0 = rarely; 3 = most of the time). This questionnaire will also be 
administered through an online link for a follow-up assessment the academic quarter after the participant 
completes her session. 
 
3.2h. Perceived stress will be assessed with the 10-item Perceived Stress Scale (PSS) (Cohen, Kamarck, 
Mermelstein, 1983), a widely used scale assessing how often events had been experienced as unpredictable, 
uncontrollable, and overwhelming over the past week (0 = never; 4 = very often). Individuals with higher 
perceived stress exhibit blunted reward-learning (Pizzagalli et al., 2007). 
 
3.2i Emotion Regulation. The 5 item self-kindness subscale from the Self-Compassion scale (Neff, 2003) and 
the 6 item rumination subscale from the Rumination and Reflection scale (Trapnell & Campbel, 1999) will be 
administered to assess levels of positive and negative emotion regulation. This will allow us to examine the 
extent to which basic reward processing is associated with regulation of emotion. 
 
3.2j. Positive Psychological Constructs. The Ego Resiliency Scale (Block & Kremen, 1996; 14 items) will be 
used to assess trait resilience, and the Mental Health Continuum Short Form (Keyes, 2002; 14 items) will be 
used to assess eudaimonic and hedonic well-being. The Mindful Attention Awareness Scale (MAAS) will be 
used to assess trait mindfulness (Brown & Ryan, 2003; 15 items). These measures will allow us to examine the 
extent to which reward processing is associated with different dimensions of psychological well-being. 
 

 
 
12
 
4. Compensation 
 
Participants will receive course credit through SONA for their participation. Participants will be told they can 
also win the summed amount of two randomly selected trials from one of the behavioral reward tasks (the 
EEfRT) and their winnings from a second reward task (the PRT).  Participants will only receive this money if 
they complete a brief online questionnaire assessing depressive symptoms, mood and state affect the subsequent 
academic quarter. Thus, participants will not receive monetary reimbursement while they are participating 
under the SONA system in the current academic quarter. Partial payment will not be offered. 
 
5. Potential Benefits of the Proposed Research to Participants 
 
There are no direct benefits. 
 
6. Importance of the Knowledge to be Gained 
 
This project will advance our understanding of the effects of stress and inflammation on anhedonia, an 
important psychological construct that is both a symptom of depression and a potential mechanism leading to 
increased risk for development of depression. Understanding factors that give rise to anhedonia will ultimately 
contribute to more specialized treatment that is targeted at specific symptoms of depression. 
 
7. Protection of Human Subjects 
 
7.1. Known or Expected Risk for Participants and Procedures to Minimize Risk 
 
7.1a. Risk to confidentiality and privacy. RARE. As in any project involving multiple sources of data, there are 
potential risks to confidentiality. For example, there is a potential risk to confidentiality if unauthorized 
individuals access subjects’ records. There may be inadvertent risks to confidentiality if questionnaires or 
interviews are misplaced or lost. In order to minimize risks to confidentiality and privacy several measures will 
be taken. All research personnel are required to take the CITI Ethics in Research with Human Subject 
certification as well as take the utmost precautions in protecting health information. All subjects are assigned a 
Research ID number, which will be the only identifier assigned to all research data. All collected materials will 
only contain this number as an identifier and will be stored in locked file cabinets or a secure freezer in the 
UCLA Health Psychology Laboratory. Only the PI and authorized study personnel will have access to the 
Research ID number. Electronic copies of research results will be stored in password protected computers and 
in a backup server only accessible to the primary investigator. To protect privacy during the laboratory session, 
the PI and/or authorized study personnel will meet all participants at the Mind-Body Laboratory at UCLA, and 
obtain informed consent in a private room. This private room will also be used to complete computer tasks and 
questionnaires. Visit 2 will occur in a private room at the CTRC. 
 
7.1b. Risks related to laboratory tasks. COMMON. It is possible that removal of blood may be associated with 
slight pain from the needle prick and/or that a bruise may develop at the site of the needle puncture.  In rare 
cases, fainting or infection may occur. All blood draws will be done using sterile procedures by a registered 
nurse to minimize these risks. There are no known risks associated with the collection of saliva.  For people 
who tend to have a dry mouth and produce little saliva, there can be some discomfort in chewing on the cotton 
cloth. It is also possible that some participants will experience some emotional discomfort during some of the 
cognitive tasks as these include the presentation of emotional stimuli (e.g., sad faces). In order to minimize risks 
related to laboratory tasks several measures will be taken. The participants will be accompanied by a trained and 
experienced research assistant during all laboratory tasks. These research staff will have experience working 
with research participants and will be trained to monitor whether the participant displays a level of discomfort 

 
 
13
that is beyond what is expected during these tasks. All research procedures will be terminated if a participant 
displays such level of discomfort. 
 
7.1c. Risks related to mental health concerns. INFREQUENT. Participants may experience discomfort when 
completing psychological questionnaires, including items pertaining to depression and anxiety. In order to 
minimize risks related to mental health concerns, all participants will be provided with information regarding 
access to mental health services.  
 
8. Data and Safety Monitoring Plan 
 
8.1 Data Monitoring Plan 
 
The PI or authorized study personnel will assign a Research ID number to each participant at the time of study 
entry. Only the PI and authorized study personnel will have access to a locked, password-protected document 
linking identifiable information to the Research ID number.  
 
All data collected will include the ID number and no identifying information. Online questionnaire data will be 
collected using the online survey platform Qualtrics. Qualtrics uses Transport Layer Security (TLS) encryption. 
Participants will be sent a personalized link that already contains their study ID number and will not be asked to 
enter personally identifiable information. This way, the online survey information will be kept separate from 
any personally identifying information. Electronic data will be stored on a secure server in the Department of 
Psychology; only the PI and authorized personnel will have access to this data. Data will be reported as 
averages and no individual participant's data will be identifiable. 
 
Biological samples will be labeled only by code number and will be stored in a -20° C freezer in a locked room 
within the PRP at the CTRC or at the UCLA Health Psychology Laboratory until assayed. Per UCLA Clinical 
Laboratory procedure for research studies, blood samples will not be identified by medical record numbers 
(Anonymous ID), and will not be entered into the PCMIS/MCCS system. 
 
Upon completion of data collection, the principal investigator will retain de-identified original paper data in a 
locked file cabinet, and all electronic data will be stored on a secure server operated by the College of Life 
Sciences and backup media in the Department of Psychology. A separate, password protected file linking each 
participant's unique PID to any identifying data will be kept by Principal Investigator in an encrypted computer. 
 
8.2 Risk Management Procedures 
 
8.2a Referral for participant depression and other psychopathology.  As part of the study, depression or distress 
in the participant may become evident during the study. Research staff will be trained to recognize signs of 
distress during the stress protocol that are beyond a normative response. If a participant evidences distress 
during the TSST, research assistants will be trained to stop the procedure and ask the participant if she desires to 
continue. If the participant does not wish to continue, research assistants will have a prepared debriefing script 
that explains that the speech task and math task were designed to elicit stress and do not actually reflect on the 
participant’s performance. They will also explain that the participant was not actually being evaluated at any 
point in time. Participants will be provided resources to obtain mental health services at the UCLA campus 
clinic, and receive the number of a 24-hour Crisis Hotline. 
 
8.2b Adverse event (AE) reporting.  All serious and unexpected adverse events will be reported to the IRB 
within 24 hours the awareness of their occurrence.  All other adverse events will be reported to the IRB in 
aggregate with annual reports.  We will monitor participants frequently as to clinical response, to reduce the 
likelihood of adverse events. 

 
 
14
 
9. Statistical Approach 
 
9.1 Sample Size Estimation 
 
Specifying an  value of .05, a sample size of 57 is required to provide 80% power to detect a significant 
indirect effect in the mediation model. Sample size estimates come from Monte Carlo power analysis using the 
software developed by Schoemann and colleagues (2017). Estimates for standard deviations and correlations 
among the predictor, mediator and outcome variable come from pilot data in our lab (unpublished) as well as 
our prior work on peripheral IL-6 and PRT performance. We assumed a moderate correlation (r = .5) between 
our predictor (TSST vs. P-TSST) and mediator (change in IL-6). 
 
9.2 Statistical Analyses Overview  
Single mediation analyses will be conducted to evaluate the hypothesis that IL-6 mediates effects of stress 
on change in performance on the EEfRT and PRT. The predictor is group assignment (TSST/P-TSST). The 
mediator variable is an IL-6 change score (IL-6 at 120 minutes minus IL-6 at baseline) with higher values 
indicating a greater increase in IL-6. The outcome variables are also change scores (post-TSST/P-TSST 
performance minus baseline performance). The mediation model provides coefficients that test the extent to 
which group assignment predicts change in IL-6 (i.e., did the stress group have a greater inflammatory response 
than the control group) and the extent to which changes in IL-6 predict changes in reward task performance 
(controlling for group assignment). The significance of the mediated effect (i.e., testing whether IL-6 mediated 
the effect of condition on reward task performance) is tested using a non-parametric bootstrap approach 
implemented using the paramed module in STATA 13.1. Using 10,000 bootstrap samples for each analysis, 
point estimates, standard errors and bias-corrected bootstrap confidence intervals will be obtained for the 
mediated effect; the mediated effect is significant if the confidence intervals do not include zero. 
 
9.3 Hypothesis Testing 
 
Hypothesis 1 proposes that increases in inflammation will statistically mediate the effect of condition (TSST 
versus P-TSST) on reward processing deficits. Mediation analyses will be conducted using the paramed module 
in STATA, which allows for the inclusion of covariates and provides non-parametric bootstrapped confidence 
intervals to test the significance of the indirect effect. Separate analyses for each of the three dependent 
variables (e.g., response bias, attentional bias scores, proportions of hard versus easy trials) will be conducted. 
 
 
 
1a. Probabilistic reward task. The reward learning task (PRT) will be administered before and after the 
TSST/P-TSST. At each assessment a response bias score will be computed as an index of reward 
responsiveness. Change in response bias is calculated by subtracting the total response bias at pre-TSST/P-
TSST from the total response bias at post-TSST/P-TSST. This change score is the outcome variable for the 
mediation analysis.  
 
 
 
1b. Effort Expenditure for Rewards Task - motivation.  The proportion of high effort trials chosen is 
calculated for the baseline assessment and for the post-TSST assessment. A change score is then calculated by 
subtracting the proportions chosen at Visit 1 from proportions chosen post-TSST/P-TSST; this change score is 
the outcome variable for the mediation model. Consistent with prior studies, change scores at each of three 
levels of probability are also calculated.  
 
 
1c. Effort Expenditure for Rewards Task - sensitivity.  Generalized estimating equations (GEEs) with a 
binary logistic model and exchangeable working correlation structure will be conducted within the stress group. 
GEEs account for correlated data, are appropriate for a binary dependent variable (i.e. likelihood of choosing 
high-effort trials), and are a standard approach for analyzing EEfRT performance on a trial by trial basis. The 

 
 
15
predictor of interest is a 2-way interaction term between reward magnitude and change in IL-6; this term 
assesses whether increases in reward magnitude predict increased choice of high effort trials less robustly in the 
context of greater increases in IL-6.   
 
 
 
1d. Dot probe task.  An attentional bias score will be created by subtracting response time to neutral 
faces from response time to happy faces. Change in attentional bias is calculated by subtracting the total 
attentional bias score at pre-TSST/P-TSST from the total attentional bias score at post-TSST/P-TSST. This 
change score is the outcome variable for the mediation analysis.  
 
 
1e. Face morphing task.  A change score for reaction time latency for detection of positive faces will be 
created by subtracting response time to positive faces at pre-TSST/P-TSST from reaction time at post-TSST/P-
TSST. This change score is the outcome variable for the mediation analysis. 
 
Hypothesis 2 proposes that vulnerability factors will moderate the association between the stress-induced 
inflammatory response and alterations in reward processing. Moderated mediation models for each of the three 
vulnerability factors (history of early adversity, trait anhedonia, current depressive symptoms) will be 
conducted using the Hayes Process Module in SPSS.  
 
 
Hypothesis 3 proposes that compared to those in the P-TSST, stressed participants will report increased negative 
and reduced positive affect immediately post stressor. Multiple regression analysis will be used to test for group 
differences in affect following the TSST/P-TSST; baseline affect will be included as a covariate and group 
assignment (TSST/P-TSST) is the predictor of interest.  Changes in positive affect are hypothesized to correlate 
with changes in reward task performance; this will be assessed with bivariate correlations between change 
scores within the stress group.  
 
 
Hypothesis 4 proposes that the degree of reward dysregulation in response to stress-induced inflammation will 
predict increases in depressive symptoms and perceived stress, and decreases in positive affect, four months 
following the experimental session. Multiple regression analyses will be conducted for participants who 
underwent stress, with change in the psychosocial measure as the outcome (study entry to 4-month follow up), 
and change in reward processing (pre to post-TSST) as the predictor.  
 
 
References 
 
Anand, D., Oehlberg, K. A., Treadway, M. T., & Nusslock, R. (2016). Effect of failure/success feedback and 
the moderating influence of personality on reward motivation. Cognition and Emotion, 30(3), 458–471. 
http://doi.org/10.1080/02699931.2015.1013088 
Anisman, H., & Matheson, K. (2005). Stress, depression, and anhedonia: Caveats concerning animal models. 
Neuroscience & Biobehavioral Reviews, 29(4–5), 525–546. 
http://doi.org/10.1016/j.neubiorev.2005.03.007 
Armstrong, T., & Olatunji, B. O. (2012). Eye tracking of attention in the affective disorders: a meta-analytic 
review and synthesis. Clinical Psychology Review, 32(8), 704–723. 
http://doi.org/10.1016/j.cpr.2012.09.004 
Aschbacher, K., Epel, E., Wolkowitz, O. M., Prather, A. A., Puterman, E., & Dhabhar, F. S. (2012). 
Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and 
future depressive symptoms. Brain, Behavior, and Immunity, 26(2), 346–52. 
http://doi.org/10.1016/j.bbi.2011.10.010 
Baskin-Sommers, A. R., & Foti, D. (2015). depressive disorder: Considering reward as a transdiagnostic 
mechanism. International Journal of Psychophysiology, 1–13. 
http://doi.org/10.1016/j.ijpsycho.2015.01.011 

 
 
16
Bedwell, J. S., Gooding, D. C., Chan, C. C., & Trachik, B. J. (2014). Anhedonia in the age of RDoC. 
Schizophrenia Research, 160(1-3), 226–227. http://doi.org/10.1016/j.schres.2014.10.028 
Berghorst, L. H., Bogdan, R., Frank, M. J., & Pizzagalli, D. A. (2013). Acute stress selectively reduces reward 
sensitivity. Frontiers in Human Neuroscience, 7, 133. http://doi.org/10.3389/fnhum.2013.00133 
Berns, G. S. (2004). Something funny happened to reward. Trends in Cognitive Sciences, 8(5), 193–194. 
http://doi.org/10.1016/j.tics.2004.03.007 
Berridge, K. C., & Kringelbach, M. L. (2008). Affective neuroscience of pleasure: reward in humans and 
animals. Psychopharmacology, 199(3), 457–480. http://doi.org/10.1007/s00213-008-1099-6 
Berridge, K. C., & Kringelbach, M. L. (2015). Pleasure Systems in the Brain. Neuron, 86(3), 646–664. 
http://doi.org/10.1016/j.neuron.2015.02.018 
Bershad, A. K., Seiden, J. A., & de Wit, H. (2016). Effects of buprenorphine on responses to social stimuli in 
healthy adults. Psychoneuroendocrinology, 63, 43–49. http://doi.org/10.1016/j.psyneuen.2015.09.011 
Block, J., & Kremen, A. M. (1996). IQ and ego-resiliency: conceptual and empirical connections and 
separateness. Journal of personality and social psychology, 70(2), 349. 
Bogdan, R., Nikolova, Y. S., & Pizzagalli, D. A. (2013). Neurogenetics of depression : A focus on reward 
processing and stress sensitivity. Neurobiology of Disease, 52, 12–23. 
http://doi.org/10.1016/j.nbd.2012.05.007 
Bogdan, R., Perlis, R. H., Fagerness, J., & Pizzagalli, D. A. (2010). The impact of mineralocorticoid receptor 
ISO/VAL genotype (rs5522) and stress on reward learning. Genes, Brain, and Behavior, 9(6), 658–67. 
http://doi.org/10.1111/j.1601-183X.2010.00600.x 
Bogdan, R., & Pizzagalli, D. A. (2006). Acute Stress Reduces Reward Responsiveness: Implications for 
Depression. Biological Psychiatry, 60(10), 1147–1154. http://doi.org/10.1016/j.biopsych.2006.03.037 
Bogdan, R., Santesso, D. L., Fagerness, J., Perlis, R. H., & Pizzagalli, D. A. (2011). Corticotropin-Releasing 
Hormone Receptor Type 1 (CRHR1) Genetic Variation and Stress Interact to Influence Reward 
Learning. The Journal of Neuroscience, 31(37), 13246–13254. 
http://doi.org/10.1523/JNEUROSCI.2661-11.2011 
Bostock, S., Hamer, M., Wawrzyniak, A. J., Mitchell, E. S., & Steptoe, A. (2011). Positive emotional style and 
subjective, cardiovascular and cortisol responses to acute laboratory stress. Psychoneuroendocrinology, 
36(8), 1175–1183. http://doi.org/10.1016/j.psyneuen.2011.02.009 
Breines, J. G., Thoma, M. V., Gianferante, D., Hanlin, L., Chen, X., & Rohleder, N. (2014). Self-compassion as 
a predictor of interleukin-6 response to acute psychosocial stress. Brain, Behavior, and Immunity, 37, 
109–114. http://doi.org/10.1016/j.bbi.2013.11.006 
Brown, K.W. & Ryan, R.M. (2003). The benefits of being present: Mindfulness and its role in psychological 
well-being. Journal of Personality and Social Psychology, 84, 822-848.  
Cabib, S., & Puglisi-Allegra, S. (2012). The mesoaccumbens dopamine in coping with stress. Neuroscience and 
Biobehavioral Reviews, 36(1), 79–89. http://doi.org/10.1016/j.neubiorev.2011.04.012 
Capuron, L. (2012). Dopaminergic Mechanisms of Reduced Basal Ganglia Responses to Hedonic Reward 
During Interferon Alfa Administration. Archives of General Psychiatry, 69(10), 1044. 
http://doi.org/10.1001/archgenpsychiatry.2011.2094 
Carpenter, L. L., Gawuga, C. E., Tyrka, A. R., Lee, J. K., Anderson, G. M., & Price, L. H. (2010). Association 
between Plasma IL-6 Response to Acute Stress and Early-Life Adversity in Healthy Adults. 
Neuropsychopharmacology, 35(13), 2617–2623. http://doi.org/10.1038/npp.2010.159 
Carver, C. S., & White, T. L. (1994). Behavioral inhibition, behavioral activation, and affective responses to 
impending reward and punishment: The BIS/BAS Scales. Journal of Personality and Social Psychology, 
67(2), 319–333. http://doi.org/10.1037/0022-3514.67.2.319 
Chapman, D. P., Dube, S. R., & Anda, R. F. (2007). Adverse childhood events as risk factors for negative 
mental health outcomes. Psychiatric Annals, 37(5), 359–364. 
Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004). Adverse 
childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective 
Disorders, 82(2), 217–225. http://doi.org/10.1016/j.jad.2003.12.013 

 
 
17
Corral-Frías, N. S., Nadel, L., Fellous, J.-M., & Jacobs, W. J. (2016). Behavioral and self-reported sensitivity to 
reward are linked to stress-related differences in positive affect. Psychoneuroendocrinology, 66, 205–
213. http://doi.org/10.1016/j.psyneuen.2016.01.012 
Corral-Frías, N. S., Nikolova, Y. S., Michalski, L. J. J., Baranger, D. a. a., Hariri,  a. R., & Bogdan, R. (2015). 
Stress-related anhedonia is associated with ventral striatum reactivity to reward and transdiagnostic 
psychiatric symptomatology. Psychological Medicine, 45(12), 2605–2617. 
http://doi.org/10.1017/S0033291715000525 
Curran, S. L., Andrykowski, M. A., & Studts, J. L. (1995). Short form of the Profile of Mood States (POMS-
SF): Psychometric information. Psychological assessment, 7(1), 80. 
Cutrona, C. E. and Russell, D. (1987). The provisions of social relationships and adaptation to stress. In W. H. 
Jones & D. Perlman (Eds.) Advances in personal relationships (Vol. 1, pp. 37-67). Greenwich, CT: JAI 
Press. 
Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to 
sickness and depression: when the immune system subjugates the brain. Nature Reviews. Neuroscience, 
9(1), 46–56. http://doi.org/10.1038/nrn2297 
Der-Avakian, A., & Markou, A. (2013). The Neurobiology of Anhedonia and Other Reward-Related Deficits. 
Trends in Neuroscience, 35(1), 68–77. http://doi.org/10.1016/j.tins.2011.11.005.The 
Der-Avakian, A., Mazei-Robison, M. S., Kesby, J. P., Nestler, E. J., & Markou, A. (2014). Enduring Deficits in 
Brain Reward Function after Chronic Social Defeat in Rats: Susceptibility, Resilience, and 
Antidepressant Response. Biological Psychiatry, 76(7), 542–549. 
http://doi.org/10.1016/j.biopsych.2014.01.013 
Dickerson, S. S., Gable, S. L., Irwin, M. R., Aziz, N., & Kemeny, M. E. (2009). Social-Evaluative Threat and 
Proinflammatory Cytokine Regulation An Experimental Laboratory Investigation. Psychological 
Science, 20(10), 1237–1244. 
Dillon, D. G., Holmes, A. J., Birk, J. L., Brooks, N., Lyons-Ruth, K., & Pizzagalli, D. a. (2009). Childhood 
Adversity Is Associated with Left Basal Ganglia Dysfunction During Reward Anticipation in 
Adulthood. Biological Psychiatry, 66(3), 206–213. http://doi.org/10.1016/j.biopsych.2009.02.019 
Dube, S. R., Felitti, V. J., Dong, M., Giles, W. H., & Anda, R. F. (2003). The impact of adverse childhood 
experiences on health problems: evidence from four birth cohorts dating back to 1900. Preventive 
Medicine, 37(3), 268–277. http://doi.org/10.1016/S0091-7435(03)00123-3 
Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2010). 
Inflammation-induced anhedonia: Endotoxin reduces ventral striatum responses to reward. Biological 
Psychiatry, 68(8), 748–754. http://doi.org/10.1016/j.biopsych.2010.06.010 
Epstein, J., Pan, H., Kocsis, J. H., Yang, Y., Butler, T., Chusid, J., … Silbersweig, D. a. (2006). Lack of ventral 
striatal response to positive stimuli in depressed versus normal subjects. American Journal of 
Psychiatry, 163(October), 1784–1790. http://doi.org/10.1176/appi.ajp.163.10.1784 
Fagundes, C. P., Glaser, R., Hwang, B. S., Malarkey, W. B., & Kiecolt-Glaser, J. K. (2013). Depressive 
symptoms enhance stress-induced inflammatory responses. Brain, Behavior, and Immunity, 31, 172–
176. http://doi.org/10.1016/j.bbi.2012.05.006 
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., ... & Marks, J. S. 
(1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of 
death in adults: The Adverse Childhood Experiences (ACE) Study. American journal of preventive 
medicine, 14(4), 245-258. 
Fletcher, K., Parker, G., Paterson, A., Fava, M., Iosifescu, D., & Pizzagalli, D. A. (2015). Anhedonia in 
melancholic and non-melancholic depressive disorders. Journal of Affective Disorders, 184, 81–8. 
http://doi.org/10.1016/j.jad.2015.05.028 
Foley, P., & Kirschbaum, C. (2010). Human hypothalamus–pituitary–adrenal axis responses to acute 
psychosocial stress in laboratory settings. Neuroscience & Biobehavioral Reviews, 35(1), 91–96. 
http://doi.org/10.1016/j.neubiorev.2010.01.010 

 
 
18
Frisch, J. U., Häusser, J. A., & Mojzisch, A. (2015). The Trier Social Stress Test as a paradigm to study how 
people respond to threat in social interactions. Frontiers in Psychology, 6. 
http://doi.org/10.3389/fpsyg.2015.00014 
Gard, D. E., Gard, M. G., Kring, A. M., & John, O. P. (2006). Anticipatory and consummatory components of 
the experience of pleasure: A scale development study. Journal of Research in Personality, 40, 1086–
1102. http://doi.org/10.1016/j.jrp.2005.11.001 
Godin, G., Shephard, R. J.. (1997) Godin Leisure-Time Exercise Questionnaire. Medicine and Science in Sports 
and Exercise. 29 June Supplement: S36-S38. 
Gold, P. W. (2015). The organization of the stress system and its dysregulation in depressive illness. Molecular 
Psychiatry, 20(1), 32–47. http://doi.org/10.1038/mp.2014.163 
Goldstein, B. L., & Klein, D. N. (2014). A review of selected candidate endophenotypes for depression. 
Clinical Psychology Review, 34(5), 417–427. http://doi.org/10.1016/j.cpr.2014.06.003 
Gotlib, I. H., Hamilton, J. P., Cooney, R. E., Singh, M. K., Henry, M. L., & Joormann, J. (2010). Neural 
processing of reward and loss in girls at risk for major depression. Archives of General Psychiatry, 
67(4), 380–387. http://doi.org/10.1001/archgenpsychiatry.2010.13 
Gotlib, I. H., Joormann, J., & Foland-Ross, L. C. (2014). Understanding Familial Risk for Depression: A 25-
Year Perspective. Perspectives on Psychological Science : A Journal of the Association for 
Psychological Science, 9(1), 94–108. http://doi.org/10.1177/1745691613513469 
Gradin, V. B., Kumar, P., Waiter, G., Ahearn, T., Stickle, C., Milders, M., … Steele, J. D. (2011). Expected 
value and prediction error abnormalities in depression and schizophrenia. Brain, 134(6), 1751–1764. 
http://doi.org/10.1093/brain/awr059 
Güth, W., Schmittberger, R., & Schwarze, B. (1982). An experimental analysis of ultimatum 
bargaining. Journal of Economic Behavior & Organization, 3(4), 367-388. 
Hannestad, J., DellaGioia, N., Ortiz, N., Pittman, B., & Bhagwagar, Z. (2011). Citalopram Reduces Endotoxin-
Induced Fatigue. Brain, Behavior, and Immunity, 25(2), 256–259. 
http://doi.org/10.1016/j.bbi.2010.10.013 
Harbaugh, W. T., Mayr, U., & Burghart, D. R. (2007). Neural responses to taxation and voluntary giving reveal 
motives for charitable donations. Science, 316(5831), 1622-1625. 
Harrison, N. A., Voon, V., Cercignani, M., Cooper, E. A., Pessiglione, M., & Critchley, H. D. (2015). A 
Neurocomputational Account of How Inflammation Enhances Sensitivity to Punishments Versus 
Rewards. Biological Psychiatry, (14), 1–9. http://doi.org/10.1016/j.biopsych.2015.07.018 
Harvey, P.-O., Pruessner, J., Czechowska, Y., & Lepage, M. (2007). Individual differences in trait anhedonia: a 
structural and functional magnetic resonance imaging study in non-clinical subjects. Molecular 
Psychiatry, 12, 703, 767–775. http://doi.org/10.1038/sj.mp.4002021 
Hasler, G., Drevets, W. C., Manji, H. K., & Charney, D. S. (2004). Discovering endophenotypes for major 
depression. Neuropsychopharmacology, 29(10), 1765–81. http://doi.org/10.1038/sj.npp.1300506 
Heim, C., & Binder, E. B. (2012). Current research trends in early life stress and depression: review of human 
studies on sensitive periods, gene-environment interactions, and epigenetics. Experimental Neurology, 
233(1), 102–11. http://doi.org/10.1016/j.expneurol.2011.10.032 
Hellhammer, J., & Schubert, M. (2012). The physiological response to Trier Social Stress Test relates to 
subjective measures of stress during but not before or after the test. Psychoneuroendocrinology, 37(1), 
119–124. http://doi.org/10.1016/j.psyneuen.2011.05.012 
Het, S., Rohleder, N., Schoofs, D., Kirschbaum, C., & Wolf, O. T. (2009). Neuroendocrine and psychometric 
evaluation of a placebo version of the “Trier Social Stress Test.” Psychoneuroendocrinology, 34(7), 
1075–1086. http://doi.org/10.1016/j.psyneuen.2009.02.008 
Het, S., Schoofs, D., Rohleder, N., & Wolf, O. T. (2012). Stress-induced cortisol level elevations are associated 
with reduced negative affect after stress: Indications for a mood-buffering cortisol effect. Psychosomatic 
Medicine, 74(1), 23–32. http://doi.org/http://dx.doi.org/10.1097/PSY.0b013e31823a4a25 

 
 
19
Het, S., & Wolf, O. T. (2007). Mood changes in response to psychosocial stress in healthy young women: 
Effects of pretreatment with cortisol. Behavioral Neuroscience, 121(1), 11–20. 
http://doi.org/10.1037/0735-7044.121.1.11 
Ho, N., & Sommers, M. (2013). Anhedonia: A Concept Analysis. Archives of Psychiatric Nursing, 27(3), 121–
129. http://doi.org/10.1016/j.apnu.2013.02.001 
Horowitz, M. Wilner, N. & Alvarez, W. (1979). Impact of Event Scale: A measure of subjective stress. 
Psychosomatic Medicine, 41, 209-218 
Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., … Wang, P. (2010). Research Domain 
Criteria (RDoC): Toward a New Classification Framework for Research on Mental Disorders. American 
Journal of Psychiatry, 167(7), 748–751. http://doi.org/10.1176/appi.ajp.2010.09091379 
Irwin, M. R., & Cole, S. W. (2011). Reciprocal regulation of the neural and innate immune systems. Nature 
Reviews. Immunology, 11(9), 625–32. http://doi.org/10.1038/nri3042 
Kashdan, T. B. (2004). The neglected relationship between social interaction anxiety and hedonic deficits: 
differentiation from depressive symptoms. Journal of Anxiety Disorders, 18(5), 719–730. 
http://doi.org/10.1016/j.janxdis.2003.08.001 
Keedwell, P. a., Andrew, C., Williams, S. C. R., Brammer, M. J., & Phillips, M. L. (2005). The neural 
correlates of anhedonia in major depressive disorder. Biological Psychiatry, 58, 843–853. 
http://doi.org/10.1016/j.biopsych.2005.05.019 
Kessler, R. C., Merikangas, K. R., & Wang, P. S. (2007). Prevalence, Comorbidity, and Service Utilization for 
Mood Disorders in the United States at the Beginning of the Twenty-first Century. Annual Review of 
Clinical Psychology, 3(1), 137–158. http://doi.org/10.1146/annurev.clinpsy.3.022806.091444 
Keyes, C. L. (2002). The mental health continuum: From languishing to flourishing in life. Journal of health 
and social behavior, 207-222. 
Kirschbaum, C., Pirke, K. M., & Hellhammer, D. H. (1993). The ‘Trier Social Stress Test’–a tool for 
investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology, 28(1-2), 76-
81. 
Kogler, L., Mueller, V. I., Chang, A., Eickhoff, S. B., Gur, R. C., & Derntl, B. (2013). Psychosocial vs . 
physiological – an ALE meta-analysis on the neural correlates of stress reactions. NeuroImage, 119, 
1328. http://doi.org/10.1016/j.neuroimage.2015.06.059 
Koo, J. W., & Duman, R. S. (2008). IL-1beta is an essential mediator of the antineurogenic and anhedonic 
effects of stress. Proceedings of the National Academy of Sciences of the United States of America, 
105(2), 751–6. http://doi.org/10.1073/pnas.0708092105 
Kuebler, U., Zuccarella-Hackl, C., Arpagaus, A., Wolf, J. M., Farahmand, F., von Känel, R., … Wirtz, P. H. 
(2015). Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and 
cytokine levels in blood of healthy men. Brain, Behavior, and Immunity, 46, 87–95. 
http://doi.org/10.1016/j.bbi.2014.12.024 
Kumar, P., Berghorst, L. H., Nickerson, L. D., Dutra, S. J., Goer, F. K., Greve, D. N., & Pizzagalli, D. a. (2014). 
Differential effects of acute stress on anticipatory and consummatory phases of reward processing. 
Neuroscience, 266, 1–12. http://doi.org/10.1016/j.neuroscience.2014.01.058 
Kumar, P., Waiter, G., Ahearn, T., Milders, M., Reid, I., & Steele, J. D. (2008). Abnormal temporal difference 
reward-learning signals in major depression. Brain, 131(8), 2084–2093. 
http://doi.org/10.1093/brain/awn136 
Lewis, A. H., Porcelli, A. J., & Delgado, M. R. (2014). The effects of acute stress exposure on striatal activity 
during Pavlovian conditioning with monetary gains and losses. Frontiers in Behavioral Neuroscience, 8. 
http://doi.org/10.3389/fnbeh.2014.00179 
Lighthall, N. R., Sakaki, M., Vasunilashorn, S., Nga, L., Somayajula, S., Chen, E. Y., … Mather, M. (2012). 
Gender differences in reward-related decision processing under stress. Social Cognitive and Affective 
Neuroscience, 7(4), 476–484. http://doi.org/10.1093/scan/nsr026 
Liu, W. H., Chan, R. C. K., Wang, L. Z., Huang, J., Cheung, E. F. C., Gong, Q. Y., & Gollan, J. K. (2011). 
Deficits in sustaining reward responses in subsyndromal and syndromal major depression. Progress in 

 
 
20
Neuro-Psychopharmacology and Biological Psychiatry, 35(FEBRUARY), 1045–1052. 
http://doi.org/10.1016/j.pnpbp.2011.02.018 
McCarthy, J. (2013). Motivation and effort in individuals with social anhedonia. Thesis, 53, 1689–1699. 
http://doi.org/10.1017/CBO9781107415324.004 
McLaughlin, K. a, Conron, K. J., Koenen, K. C., & Gilman, S. E. (2010). Childhood adversity, adult stressful 
life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a 
population-based sample of adults. Psychological Medicine, 40(10), 1647–1658. 
http://doi.org/10.1017/S0033291709992121 
Miller, G. A., & Rockstroh, B. (2013). Endophenotypes in Psychopathology Research: Where Do We Stand? 
Annual Review of Clinical Psychology, 9(1), 177–213. http://doi.org/10.1146/annurev-clinpsy-050212-
185540 
Miller, G. E., & Chen, E. (2010). Harsh family climate in early life presages the emergence of a 
proinflammatory phenotype in adolescence. Psychological Science, 21(6), 848–56. 
http://doi.org/10.1177/0956797610370161 
Moieni, M., Irwin, M. R., Jevtic, I., Olmstead, R., Breen, E. C., & Eisenberger, N. I. (2015). Sex Differences in 
Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex 
Differences in Depression. Neuropsychopharmacology, 40(7), 1709–1716. 
http://doi.org/10.1038/npp.2015.17 
Morris, B. H., & Rottenberg, J. (2015). Heightened Reward Learning Under Stress in Generalized Anxiety 
Disorder : A Predictor of Depression Resistance ?, 124(1), 115–127. 
Neff, K.D. (2003). Development and validation of a scale to measure self-compassion. Self and Identity. 2, 223-
250  
Nestler, E. J., & Carlezon, W. A. (2006). The mesolimbic dopamine reward circuit in depression. Biological 
Psychiatry, 59(12), 1151–9. http://doi.org/10.1016/j.biopsych.2005.09.018 
Oei, N. Y. L., Both, S., van Heemst, D., & van der Grond, J. (2014). Acute stress-induced cortisol elevations 
mediate reward system activity during subconscious processing of sexual stimuli. 
Psychoneuroendocrinology, 39, 111–120. http://doi.org/10.1016/j.psyneuen.2013.10.005 
Ossewaarde, L., Qin, S., Van Marle, H. J. F., van Wingen, G. A., Fernández, G., & Hermans, E. J. (2011). 
Stress-induced reduction in reward-related prefrontal cortex function. NeuroImage, 55(1), 345–52. 
http://doi.org/10.1016/j.neuroimage.2010.11.068 
Pabst, S., Brand, M., & Wolf, O. T. (2013). Stress and decision making: A few minutes make all the difference. 
Behavioural Brain Research, 250, 39–45. http://doi.org/10.1016/j.bbr.2013.04.046 
Pace, T. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller, A. H., & Heim, C. M. 
(2006). Increased stress-induced inflammatory responses in male patients with major depression and 
increased early life stress. American Journal of Psychiatry. Retrieved from 
http://ajp.psychiatryonline.org/doi/abs/10.1176/ajp.2006.163.9.1630 
Pechtel, P., Dutra, S. J., Goetz, E. L., & Pizzagalli, D. A. (2013). Blunted reward responsiveness in remitted 
depression. Journal of Psychiatric Research, 47(12), 1864–1869. 
http://doi.org/10.1016/j.jpsychires.2013.08.011 
Pechtel, P., & Pizzagalli, D. A. (2011). Effects of early life stress on cognitive and affective function: An 
integrated review of human literature. Psychopharmacology, 214(1), 55–70. 
http://doi.org/10.1007/s00213-010-2009-2 
Pizzagalli, D. a., Bogdan, R., Ratner, K. G., & Jahn, A. L. (2007). Increased perceived stress is associated with 
blunted hedonic capacity: Potential implications for depression research. Behaviour Research and 
Therapy, 45(11), 2742–2753. http://doi.org/10.1016/j.brat.2007.07.013 
Pizzagalli, D. A. (2014). Depression, stress, and anhedonia: toward a synthesis and integrated model. Annual 
Review of Clinical Psychology, 10, 393–423. http://doi.org/10.1146/annurev-clinpsy-050212-185606 
Pizzagalli, D. A., Iosifescu, D., Hallett, L. A., Ratner, K. G., & Fava, M. (2008). Reduced hedonic capacity in 
major depressive disorder: Evidence from a probabilistic reward task. Journal of Psychiatric Research, 
43(1), 76–87. http://doi.org/10.1016/j.jpsychires.2008.03.001 

 
 
21
Pizzagalli, D. A., Jahn, A. L., & O’Shea, J. P. (2005). Toward an objective characterization of an anhedonic 
phenotype: a signal-detection approach. Biological Psychiatry, 57(4), 319–27. 
http://doi.org/10.1016/j.biopsych.2004.11.026 
Putman, P., Antypa, N., Crysovergi, P., & van der Does, W. A. J. (2010). Exogenous cortisol acutely influences 
motivated decision making in healthy young men. Psychopharmacology, 208(2), 257–263. 
http://doi.org/10.1007/s00213-009-1725-y 
Radloff, L. S. (1977). The CES-D Scale A Self-Report Depression Scale for Research in the General 
Population. Applied Psychological Measurement, 1(3), 385–401. 
http://doi.org/10.1177/014662167700100306 
Repetti, R. L., Taylor, S. E., & Seeman, T. E. (2002). Risky families: family social environments and the mental 
and physical health of offspring. Psychological Bulletin, 128(2), 330–366. 
Riga, D., Theijs, J. T., De Vries, T. J., Smit, A. B., & Spijker, S. (2015). Social defeat-induced anhedonia: 
effects on operant sucrose-seeking behavior. Frontiers in Behavioral Neuroscience, 9. 
http://doi.org/10.3389/fnbeh.2015.00195 
Rohleder, N. (2014). Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosomatic 
Medicine, 76(3), 181–9. http://doi.org/10.1097/PSY.0000000000000049 
Rømer Thomsen, K., Whybrow, P. C., & Kringelbach, M. L. (2015). Reconceptualizing anhedonia: novel 
perspectives on balancing the pleasure networks in the human brain. Frontiers in Behavioral 
Neuroscience, 9, 49. http://doi.org/10.3389/fnbeh.2015.00049 
Rommelfanger, K. S., & Wichmann, T. (2010). Extrastriatal dopaminergic circuits of the basal ganglia. 
Frontiers in Neuroanatomy, 4, 139. http://doi.org/10.3389/fnana.2010.00139 
Russo, S., & Nestler, E. (2013). The brain reward circuitry in mood disorders. Nature Reviews Neuroscience, 
14(September), 609–625. http://doi.org/10.1038/nrn3381 
Santesso, D. L., Evins, A. E., Frank, M. J., Cowman Schetter, E. M., Bogdan, R., & Pizzagalli, D. A. (2009). 
Single Dose of a Dopamine Agonist Impairs Reinforcement Learning in Humans: Evidence from Event-
related Potentials and Computational Modeling of Striatal-Cortical Function. Human Brain Mapping, 
30(7), 1963–1976. http://doi.org/10.1002/hbm.20642 
Sescousse, G., Caldú, X., Segura, B., & Dreher, J. C. (2013). Processing of primary and secondary rewards: A 
quantitative meta-analysis and review of human functional neuroimaging studies. Neuroscience and 
Biobehavioral Reviews, 37, 681–696. http://doi.org/10.1016/j.neubiorev.2013.02.002 
Scheier, M. F., Carver, C. S., & Bridges, M. W. (1994). Distinguishing optimism from neuroticism (and trait 
anxiety, self-mastery, and self-esteem): A re-evaluation of the Life Orientation Test. Journal of 
Personality and Social Psychology, 67, 1063-1078.  
Sherdell, L., Waugh, C. E., & Gotlib, I. H. (2012). Anticipatory Pleasure Predicts Motivation for Reward in 
Major Depression. Journal of Abnormal Psychology, 121(1), 51–60. http://doi.org/10.1037/a0024945 
Slavich, G. M., & Irwin, M. R. (2014). From Stress to Inflammation and Major Depressive Disorder: A Social 
Signal Transduction Theory of Depression. Psychological Bulletin. http://doi.org/10.1037/a0035302 
Snaith, R. P., Hamilton, M., Morley, S., Humayan, A., Hargreaves, D., & Trigwell, P. (1995). A scale for the 
assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. The British Journal of Psychiatry, 
167(1), 99–103. http://doi.org/10.1192/bjp.167.1.99 
Southwick, S. M., & Vythilingam, M. (2005). The psychobiology of depression and resilience to stress: 
implications for prevention and treatment. Annual Review of Clinical Psychology, 1(1), 255–291. 
http://doi.org/10.1146/annurev.clinpsy.1.102803.143948 
Steptoe, A., Hamer, M., & Chida, Y. (2007). The effects of acute psychological stress on circulating 
inflammatory factors in humans: A review and meta-analysis. Brain, Behavior, and Immunity, 21(7), 
901–912. http://doi.org/10.1016/j.bbi.2007.03.011 
Telzer, E. H., Fuligni, A. J., Lieberman, M. D., & Galván, A. (2014). Neural sensitivity to eudaimonic and 
hedonic rewards differentially predict adolescent depressive symptoms over time. Proceedings of the 
National Academy of Sciences of the United States of America, 111(18), 6600–5. 
http://doi.org/10.1073/pnas.1323014111 

 
 
22
Thomsen, K. R. (2015). Measuring anhedonia: impaired ability to pursue, experience, and learn about reward. 
Frontiers in Psychology, 6, 1409. http://doi.org/10.3389/fpsyg.2015.01409 
Thompson, E. R. (2007). Development and validation of an internationally reliable short-form of the positive 
and negative affect schedule (PANAS). Journal of Cross-Cultural Psychology, 38(2), 227-242. 
Tottenham, N., Tanaka, J. W., Leon, A. C., McCarry, T., Nurse, M., Hare, T. A., … Nelson, C. (2009). The 
NimStim set of facial expressions: Judgments from untrained research participants. Psychiatry 
Research, 168(3), 242–249. http://doi.org/10.1016/j.psychres.2008.05.006 
Trapnell, P. D., & Campbell, J. D. (1999). Private self-consciousness and the five factor model of personality: 
Distinguishing rumination from reflection. Journal of Personality and Social Psychology, 76(2), 184-
304. 
Treadway, M. T., Buckholtz, J. W., Cowan, R. L., Woodward, N. D., Li, R., Ansari, M. S., … Zald, D. H. 
(2012). Dopaminergic mechanisms of individual differences in human effort-based decision-making. 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 32(18), 6170–6176. 
http://doi.org/10.1523/JNEUROSCI.6459-11.2012 
Treadway, M. T., Buckholtz, J. W., Schwartzman, A. N., Lambert, W. E., & Zald, D. H. (2009). Worth the 
“EEfRT”? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. 
PloS One, 4(8), e6598. http://doi.org/10.1371/journal.pone.0006598 
Treadway, M. T., & Zald, D. H. (2011). Reconsidering anhedonia in depression: Lessons from translational 
neuroscience. Neuroscience and Biobehavioral Reviews, 35(3), 537–555. 
http://doi.org/10.1016/j.neubiorev.2010.06.006 
van den Bos, R., Harteveld, M., & Stoop, H. (2009). Stress and decision-making in humans: Performance is 
related to cortisol reactivity, albeit differently in men and women. Psychoneuroendocrinology, 34(10), 
1449–1458. http://doi.org/10.1016/j.psyneuen.2009.04.016 
Vrieze, E., Ceccarini, J., Pizzagalli, D. A., Bormans, G., Vandenbulcke, M., Demyttenaere, K., … Claes, S. 
(2013). Measuring extrastriatal dopamine release during a reward learning task. Human Brain Mapping, 
34(3), 575–586. http://doi.org/10.1002/hbm.21456 
Vrieze, E., Pizzagalli, D. A., Demyttenaere, K., Hompes, T., Sienaert, P., De Boer, P., … Claes, S. (2013). 
Reduced reward learning predicts outcome in major depressive disorder. Biological Psychiatry, 73(7), 
639–645. http://doi.org/10.1016/j.biopsych.2012.10.014 
Wardle, M. C., Treadway, M. T., Mayo, L. M., Zald, D. H., & de Wit, H. (2011). Amping up effort: effects of 
d-amphetamine on human effort-based decision-making. The Journal of Neuroscience: The Official 
Journal of the Society for Neuroscience, 31(46), 16597–16602. 
http://doi.org/10.1523/JNEUROSCI.4387-11.2011 
Watson, D., & Clark, L. A. (1999). The PANAS-X: Manual for the Positive and Negative Affect Schedule - 
Expanded Form. Department of Psychological & Brain Sciences Publications. Retrieved from 
http://ir.uiowa.edu/psychology_pubs/11 
Watson, D., Clark, L. A., Weber, K., Assenheimer, J. S., Strauss, M. E., & McCormick, R. A. (1995). Testing a 
tripartite model: II. Exploring the symptom structure of anxiety and depression in student, adult, and 
patient samples. Journal of Abnormal Psychology, 104(1), 15–25. http://doi.org/10.1037/0021-
843X.104.1.15 
Waugh, C. E., & Gotlib, I. H. (2008). Motivation for reward as a function of required effort: Dissociating the 
“liking” from the “wanting” system in humans. Motivation and Emotion, 32(4), 323–330. 
http://doi.org/10.1007/s11031-008-9104-2 
Winer, E. S., & Salem, T. (2016). Reward devaluation: Dot-probe meta-analytic evidence of avoidance of 
positive information in depressed persons. Psychological Bulletin, 142(1), 18–78. 
http://doi.org/10.1037/bul0000022 
Xie, W., Yan, C., Ying, X., Zhu, S., Shi, H., Wang, Y., … Chan, R. C. K. (2014). Domain-specific hedonic 
deficits towards social affective but not monetary incentives in social anhedonia. Scientific Reports, 4, 
4056. http://doi.org/10.1038/srep04056 

 
 
23
Yang, X., Huang, J., Zhu, C., Wang, Y., Cheung, E. F. C., Chan, R. C. K., & Xie, G. (2014). Motivational 
deficits in effort-based decision making in individuals with subsyndromal depression, first-episode and 
remitted depression patients. Psychiatry Research, 220(3), 874–882. 
http://doi.org/10.1016/j.psychres.2014.08.056 
Yirmiya, R., Pollak, Y., Morag, M., Reichenberg, A., Barak, O., Avitsur, R., … Pollmächer, T. (2000). Illness, 
Cytokines, and Depression. Annals of the New York Academy of Sciences, 917(1), 478–487. 
http://doi.org/10.1111/j.1749-6632.2000.tb05412.x 
Yoon, K. L., Joormann, J., & Gotlib, I. H. (2009). Judging the Intensity of Facial Expressions of Emotion: 
Depression-Related Biases in the Processing of Positive Affect. Journal of Abnormal Psychology, 
118(1), 223–228. http://doi.org/10.1037/a0014658