The Effect of Acute Citalopram on Self-referential Emotional Processing and Social Cognition in Healthy Volunteers
Phase: NA
Conditions: Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder, Mental Disorder, Antidepressive Agents, Cognition
Sponsor: University of Oxford

 
 
The effect of acute citalopram on self-referential emotional processing and social 
cognition in healthy volunteers 
 
NCT Number: Not yet available 
 
Date: 23/09/19 
 
 
 

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1. Study Information 
 
1.1 Purpose and Academic Rationale 
 
Antidepressants are thought to operate by changing the way patients process emotional 
information1. After a single dose of citalopram or fluoxetine healthy volunteers have been 
found to display an increased recognition of happy facial expressions and a reduced 
recognition of sad faces, in the absence of changes in mood 2. Studies using depressed 
participants have produced similar results3.  
 
However, there has been comparatively little research on changes in emotional processing 
biases about the self following antidepressant administration. Sense of self has been 
proposed as fundamental for mental health, with self-schemas acting as a focus through 
which valence and reward influenced perception, memory and decision-making 4. 
Antidepressants may increase learning of positive information about the self, potentially 
remediating negative self-schema and subsequently reducing depression symptoms.  
 
In this study, we aim to examine whether acute administration of citalopram is associated 
with an increase in positive emotional learning biases about the self. Using a parallel-group 
double-blind design, participants will be randomised to receive either an acute dose of 
citalopram or placebo. Participants will then complete a number of widely used computer-
based cognitive tasks measuring emotional processing biases.  
 
Identifying early changes in cognition and behaviour following antidepressant treatment will 
increase our knowledge of how antidepressants operate, and provide putative targets to 
identify early response to antidepressants.  
 
1.2 Hypotheses 
 
H1 Social Evaluation Learning  
Participants administered citalopram will display a positive bias towards the self compared 
to participants administered a placebo, as indicated by fewer errors made before learning 
the like rule compared to the dislike rule. This effect will be strongest when learning about 
the self, compared to when learning about the friend or stranger. 
 
H2 Self Associative Learning 
Participants administered citalopram will show a greater prioritisation of learning self-
related stimuli compared to those administered a placebo, as measured by faster reaction 
times and greater accuracy when matching neutral shapes to self-related stimuli, than 
stimuli related to a friend or a stranger.  
 
H3 Reward Associative Learning 
Participants administered citalopram will show a greater prioritisation of higher levels of 
reward compared to those administered a placebo, as measured by faster reaction times 
and greater accuracy when matching neutral shapes to high-reward stimuli, than stimuli 
related to medium and low levels of reward.  
 

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H4 Valence Associative Learning 
Participants administered citalopram will show a greater prioritisation of positive stimuli 
compared to those administered a placebo, as measured by faster reaction times and 
greater accuracy when matching neutral shapes to positive (happy) stimuli, than stimuli 
related to neutral or negative (sad) stimuli.  
 
H5 Social Cooperation 
Participants administered citalopram will show greater levels of social cooperation 
compared to those administered a placebo, as measured by a greater proportion of 
cooperative behaviours in the prisoner’s dilemma task. 
 
H6 Self-Esteem Go/No-Go Task 
Participants administered citalopram will show a greater implicit positive self-esteem 
compared to those administered a placebo, as measured by a greater sensitivity towards 
categorising positive words about the self and reduced sensitivity towards categorising 
negative words about the self.  
 
This effect will be strongest when categorising words about the self; there will be smaller 
differences between participants administered citalopram versus placebo in sensitivity 
towards categorising positive and negative words with others. 
 
H7 Emotional Categorisation and Recall 
Participants administered citalopram will categorise a greater number of positive words and 
a fewer number of negative words as describing themselves compared to those 
administered a placebo. This effect will be strongest when categorising words about the 
self; there will be smaller differences between groups in the number of positive and 
negative words categorised about others.  
 
Participants administered citalopram will recall a greater number of positive words and a 
fewer number of negative words about the self. This effect will be strongest when recalling 
words about the self; there will be smaller differences between groups in the number of 
positive and negative words recalled about others. 
 
2. Sampling Plan 
 
2.1 Data Collection Procedures 
2.1.1 Recruitment 
Participants will be recruited by word of mouth, emails to departmental mailing lists, and 
posters located in University of Oxford Departments. Adverts will be displayed in Junior and 
Middle Common Rooms, Colleges and University Departments and local community 
buildings. Adverts will also be placed on local information websites (e.g. Daily Info, Oxford 
University Gazette), newspapers, local magazines, and on the lab webpage, Facebook page, 
and Twitter account. The adverts will contain brief information about the inclusion criteria 
for the study, as well as contact details for the named researchers.  
 
Participants will also be recruited via advertisement through Oxford Brookes, following 
approval from Oxford Brookes University Research Ethics Committee. The following 

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additional statement will be inserted into any recruitment documents for Oxford Brookes 
students and/or staff: "Oxford Brookes University has knowledge of this study and has 
permitted recruitment at the University. In the event of any questions about the study, 
please contact the researchers in the first instance. Should you need to contact anyone at 
Oxford Brookes about this further, please email: ethics@brookes.ac.uk". 
 
2.1.2 Inclusion/Exclusion Criteria 
 
Inclusion 
 Male or Female 
 Aged 18 -45 
 Fluent in written and spoken English at a sufficient level to understand and complete 
the tasks 
 Body Mass Index (BMI) 18-30 
 Participant is willing and able to give informed consent for participation in the study 
 Not currently taking any regular medications (expect the contraceptive pill) 
Exclusion 
 Any past or current Axis 1 DSM-V psychiatric disorder 
 Current use of psychoactive medication (except the contraceptive pill, the Depo-
Provera injection or the progesterone implant) 
 Current or past history of drug or alcohol dependency 
 History of current significant neurological condition (e.g. epilepsy) 
 Known hypersensitivity to the study drug 
 Currently pregnant or breast feeding 
 Previous participation in a study that uses the same or similar computer tasks as 
those used in the present study 
 Previous participation in a study that involves the use of a medication within the last 
three months 
 Significant medical condition 
 Smokers consuming > 5 cigarettes per day 
 Individuals consuming > 6 caffeinated drinks per day 
 Lactose Intolerance (as the placebo contains lactose) 
 
2.1.3 Study Timeline 
 
Prior to taking part in the study participants will be asked to complete a screening session, 
lasting a maximum of two hours. In this screening session participants will be asked to 
provide demographic information (name, gender, age, occupation, ethnicity, highest 
education level obtained, contact details). Participants will also be asked whether they are 
fluent in English, their first language, whether they smoke (and how much if yes), their 

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approximate alcohol consumption per week, their maximum alcohol consumption on a 
single occasion, and their average number of caffeinated drinks per day. To ensure eligibility 
participants will be asked whether they have taken part in any studies at the Departments 
of Psychiatry or Psychology before, and whether they have taken part in a study involving a 
drug or medicine before. The participants’ height and weight will be measured, to calculate 
their Body Mass Index (BMI). Participants will be asked whether they have experienced any 
significant medical problems. To ensure participants are not taking any concomitant 
medication participants will be asked whether they are currently taking any medication or 
street drugs. Female participants will be asked whether they are currently pregnant, trying 
to become pregnant or breastfeeding, and about their menstrual cycle. To ensure 
participants are not currently experiencing any psychiatric disorder the structured clinical 
interview for DSM-V axis 1 disorders will be administered. Participants will also be asked 
about their personal and family history of psychiatric disorders. (Appendix E: screening form 
to be completed by the researcher). 
 
Research visits will take place no later than four weeks following the screening. In the event 
that this timeframe is exceeded the screening procedure will be repeated.  
 
Following the screening, eligible participants will be randomised to receive either a single 
20mg oral dose of citalopram or a matched placebo tablet using an online randomisation 
tool.  
 
On the day of the research visit participants will be asked to eat only a light meal prior to 
their appointment. Upon their arrival participants will be asked to complete a number of 
self-administered questionnaires to measure baseline mood: 
- 
Patient Health Questionnaire (PHQ-9) 
- 
Beck Depression Inventory (BDI-II) 
- 
Generalised Anxiety Disorder Questionnaire (GAD-7) 
- 
Brief Fear of Negative Evaluation Scale (BFNE) 
- 
Positive and Negative Affect Schedule (PANAS) 
- 
Eysenck Personality Questionnaire Abbreviated (EPQR-A) 
- 
State and Trait Anxiety Inventory (STAI) 
- 
Visual Analogue Scales measuring subjective state (happy, sad, disgusted, angry, 
frightened, anxious and alert) 
- 
Side-Effects Questionnaire (to determine baseline bodily symptoms / ‘side-effects’) 
Female participants will also be asked to provide another urine sample for a pregnancy test 
to ensure eligibility is continued following the screening visit. They will then be administered 
the medication and asked to rest for three hours. Following the rest period participants will 
again be asked to complete the state self-administered questionnaires outlined previously 
(the PANAS scale, the State subscale of the State Trait Anxiety Inventory (STAI-S), visual 
analogue scales measuring subjective state and the side effects questionnaire) before 
completing the cognitive tasks outlined below. 
 
- 
Social Evaluation Learning5: Participants will be asked to learn how much the 
computer likes them, their friend, and a stranger. In each referential condition 

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participants are presented with positive-negative word pairs and are asked to select 
the word which they feel most represents the computer personas’ attitude. 
Participants are given feedback concerning their selection’s accuracy (correct or 
incorrect) and based on this feedback learn whether the computer likes the person. 
Feedback is manipulated to create two rules, ‘like’ (60-80% of positive words 
correct) or ‘dislike’ (20-40% of positive words correct). 
- 
Associative Learning Task6-8: Participants will be asked to match neutral shapes with 
stimuli relating to the self (self, friend, stranger), reward (£1, £3, £9) and valence 
(happy facial expression, neutral facial expression, sad facial expression) in three 
separate tasks. Participants are instructed at the beginning of the task that particular 
words/pictures belong to particular shapes. Randomised word/picture-shape pairs 
are then presented briefly on the screen, and participants are asked to indicate 
whether these presentations match with the pairings presented at the beginning of 
the task.  
- 
Prisoner’s Dilemma Task9, 10: Participants are asked to invest points in each round in 
a cooperative or non-cooperative manner with a computer simulated ‘other player’, 
and earn points dependent upon their choice. The proportion of cooperative 
behaviours will be examined.  
- 
Self-Esteem Go/No-Go Association Task11 : In this task participants will be asked to 
categorise characteristics (positive and negative) and referential words (self and 
other) into predetermined categories, by pressing the spacebar if the presented 
word belongs to the category being tested.  
- 
Emotional Categorisation and Recall: Participants will be asked to indicate whether 
characteristics describe themselves and an ‘other’. In each referential condition 
participants will be presented with 20 positive and 20 negative characteristics, each 
displayed for 500 ms. Participants will be asked to indicate whether these words 
describe themselves/the other (yes or no) using the keyboard. They will then be 
asked to recall as many characteristics they can in 2 minutes. 
Following completion of these tasks participants will again be asked to complete the PANAS 
scale, the State subscale of the State Trait Anxiety Inventory (STAI-S), visual analogue scales 
measuring subjective state and the side effects questionnaire. Finally, participants will be 
asked to guess which treatment they received to measure the success of blinding.  
This visit will last a maximum of 5 hours in total (including the three hour rest period). 
 
2.2 Sample Size and Rationale 
Previously, the effect of citalopram on emotional processing has been investigated in 
healthy volunteers using a facial expression recognition task.  On the facial expression 
recognition task, one of the main outcome variables is accuracy at recognising fearful facial 
expressions. A sample size of 22 per group would provide 90% power to detect changes of 
the magnitude of those we have seen in a previous antidepressant healthy volunteer study 
[drug mean 10.64 (SD 9.77) vs. placebo mean 3.36 (SD 5.96)12]. 44 participants will therefore 
be recruited (22 per group). 

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3. Variables 
 
3.1 Manipulated Variables 
Participants will be randomly assigned to be administered a single acute dose of citalopram 
or placebo. 
 
3.1.1. Citalopram 
Participants randomised to the citalopram group will be administered a single acute oral 20 
mg dose of citalopram, using tablets encapsulated in opaque capsules. Citalopram is a 
licensed drug that is widely used to treat depressive illness. 
 
3.1.2 Placebo 
Participants will be administered one lactose placebo tablet encapsulated in opaque 
capsules. 
 
3.2 Measured Variables 
 
3.2.1 Social Evaluation Learning- 
This task has been previously used by the research group13, 14. 
 
Participants learning of evaluations (i.e. others’ perceptions) in social interactions will be 
measured using a cognitive test on E-Prime. This is a reinforcement learning task within a 
social context, adapted from previous versions to incorporate an additional referential 
condition 5, 15. Participants are presented with word pairs and are asked to select the word 
which they feel most represents the computer personas’ attitudes. No time limit is imposed 
on word selection. Participants are given feedback concerning their selection’s accuracy 
(presented for 2000 ms), and based on this, must learn the computer’s attitude. 
 
Referential condition will be manipulated to reflect learning of social evaluations towards 
the self, a friend and a stranger. Feedback contingencies (the proportion of positive words 
that are ‘correct’) will also be manipulated throughout with trials corresponding to 20%, 
40%, 60%, and 80%. Participants will therefore learn varying levels of positive ‘like’ rules (60, 
80%) and negative ‘dislike’ rules (20, 40%). There will 12 blocks, corresponding to each 
possible rule-condition combination (three referential conditions, four rules), with 24 trials 
in each. Referential condition will be randomised.  
Accuracy of responses (proportion correct in each rule-set) and reaction times (in ms) will 
be measured. Ability to acquire the stimulus feedback association (i.e., to learn the rules) 
will be assessed by the number of errors made before reaching the criterion of eight 
consecutive rule-congruent responses. These outcomes will be collapsed across the differing 
levels of like (60%, 80%) and dislike (20%, 40%) to create overall positive ‘like’ and negative 
‘dislike’ rules. 
At the end of each block participants will be asked to provide a global rating of how much 
the computer liked them, their friend and the stranger, using a visual analogue scale ranging 
from ‘Complete Dislike’ (0) to ‘Complete Like’ (100). At the end of each of the condition 
blocks participants will be asked to make an overall global rating.  
 

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We also aim to examine how participants incorporate learned evaluations into their 
perception of themselves, their friend and the stranger. At the beginning of each block of 
referential condition participant’s will be asked ‘How do you feel about [yourself / friend / 
stranger]?’. After the global rating measure in each block participants will be asked ‘How 
does this make you feel about [yourself / friend / stranger]?’. Finally, at the end of each 
referential block participants will be asked ‘How do you now feel about [yourself / friend / 
stranger?’. A visual analogue scale ranging from Very bad (0) to Very good (100) will be used 
for each of these questions. 
 
 
 
Figure 1 
Social Evaluation Learning Task Procedure 
 
3.2.2 Associative Learning 
This task has been previously used by the research group13, 14. 
 
Three tasks will be used to examine different aspects of associative learning (self, reward 
and valence). These tasks have been adapted from Sui, Ohrling and Humphreys (2016)8. 
They were created using E-Prime v.2. Participants will undergo 9 practice trials, and two 
blocks of 60 testing trials, for each task. 
 
Accuracy of responses (proportion correct in each condition) and reaction times (in ms) will 
be measured for each task. 
 
3.2.2.1 Self 
Referential condition will be manipulated to measure salience of self-related information, 
compared to information about a chosen friend and a stranger.  

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In this task participants are told that they will learn to associate words relating to ‘self’, 
‘friend’ and ‘stranger’ with three different shapes: a triangle, a square, and a circle. The 
words will be personalised to each participant (i.e. the word ‘self’ will be replaced with the 
participants’ first name). Word-shape pairs are randomised. Participants are then presented 
with various combinations of these word-shape pairings and asked to press the ‘n’ or ‘m’ 
key to indicate whether these match with what they have previously learnt. In each trial a 
fixation point is displayed for 2000 ms, followed by a word-shape pairing for 100 ms. 
Participants must provide a response within 1100 ms. Feedback, displayed for 500 ms, is 
provided for each trial. At the end of each block participants are informed of their accuracy 
(% correct responses) for that block.  
 
3.2.2.2 Reward 
The same procedure as outline the self associative learning task will be used for the reward 
condition, but varying levels of monetary values (e.g. High £9, Medium £3, Low £1) will 
instead be used instead of words relating to the self, friends and strangers. Again, these 
monetary values will be paired with three different shapes (pentagon, oval, diamond) and 
participants will be asked to indicate whether these match with what they have initially 
learnt. Participants will receive a monetary reward dependent on their task performance for 
each shape. To calculate this the number of words correct for the shape will be divided by 
the number of trials completed for the shape, and multiplied by the corresponding value of 
the label paired with the shape (e.g. £1, £3 or £9). This will be calculated for each shape and 
added together to ascertain the reward the participant will receive. 
 
3.2.2.3 Valence 
In the valence task varying intensities of cartoon facial expressions (e.g. sad, neutral, happy) 
will be paired with shapes (hexagon, rectangle, star). Again various combinations of these 
pairings will be presented and participants will be asked to indicate whether this matches 
with what they have previously learnt. 
 
 

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Figure 2 
Examples of instructions, matching (the shape-label combination matches the instructions) trials, and non-
matching (the shape-label combination does not match the instructions) trials in the three variations of the 
associative learning task 
 
3.2.4 Prisoner’s Dilemma Task 
An iterated prisoner’s dilemma task will be used to measure cooperative behaviour using 
the procedure outlined by Rilling et al9 and Wood et al10. In this task participants are asked 
to invest points in each round in a cooperative or non-cooperative manner with a computer 
simulated ‘other player’. Participants earn points depending upon their and the other 
player’s choice. Each round has four possible outcomes: (1) both players cooperate, (2) the 
participant cooperates but the other player does not cooperate, (3) the participant does not 
cooperate but the other player does cooperate, (4) both players do not cooperate. Payoffs 
are structured so that maximum reward is obtained if the participant chooses not to 
cooperate while the other player chooses to cooperate. However, maximum loss occurs if 
the participant chooses to cooperate and the other player does not. In each round 
participants are shown a 2 x 2 matrix demonstrating these outcomes, and are asked to 
choose whether to cooperate or not cooperate.  
 
The task will be completed in two blocks; in one block the other player will initially choose 
to cooperate, while in another block the other player will initially choose to not cooperate. 
Order of blocks will be counterbalanced. Each player will independently choose to either 
cooperate or not cooperate (i.e. the participant will not be informed of the other player’s 
choice until they have made their selection), before being shown the other’s choice and the 
resulting payoff. After the initial response the other player will follow a ‘tit for tat’ strategy, 
mirroring the choice of the participant (i.e. if the participant chooses to cooperate in the 
previous round the other player will cooperate in the next round and vice versa). 24 trials 
will be completed per block. Participants will also complete a training trial at the beginning 
of the task to ensure their understanding. 
 
3.2.5 Self-Esteem Go/No-Go Task 
This task has been previously used by the research group13. 
 
To measure implicit self-schema a go/no-go task will be completed using Inquisit Lab. This 
will follow the procedure outlined by Gregg and Sedikides11, but will be adapted to use the 
64 positive-negative characteristic word-pairs used in the social evaluation learning task, 
rather than overall positive or negative words.  
 
Participants will be asked to categorise characteristics (positive and negative) and 
referential words (self and other) into predetermined categories, by pressing the spacebar if 
the presented word belongs to the category being tested. Response feedback is given. In the 
training phase participants are asked to categorise words belonging to single categories (e.g. 
positive, negative, self, other). There will be 20 trials for each category. In the test phase 
participants are asked to categorise words belonging to paired categories (e.g. positive OR 

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self, positive OR other, negative OR self, negative OR other). There will be 16 practice trials 
and 48 test trials for each paired combination of categories. A response timeout of 600 ms 
will be applied. Block order will be randomised. 
 
Responses in the go/no go association task will be categorised into ‘hits’ (correctly 
categorising the word as belonging to the target category), ‘misses’ (incorrectly categorising 
the word as not belonging to the target category), correct rejections (correctly categorising 
the word as not belonging to the target category) and false alarms (incorrectly categorising 
the word as belonging to the target category). Reaction times will also be recorded. 
 
3.2.6. Emotional Categorisation and Recall 
This task has been previously used by the research group14. 
 
Participants will be asked to indicate whether characteristics describe themselves and an 
‘other’. In each referential condition participants will be presented with 20 positive and 20  
negative characteristics, each displayed for 500 ms. Participants will be asked to indicate 
whether these words describe themselves/the other (yes or no) using the ‘k’ or ‘j’ keys.  The 
allocation of key commands to responses (e.g. whether ‘k’ or ‘j’ indicates yes or no) will be 
counter-balanced across participants, but will remain consistent within participants across 
time-points. Participants will then be asked to recall as many characteristics they can in 2 
minutes. Order of referential condition will be randomised. The characteristics used will be 
randomly assigned to each referential condition. Different words will be used to those in the 
social evaluation learning task. Number of accurate responses (hits) and incorrect 
recollections (intrusions) will be recorded. 
 
3.2.7 State Mood 
The Positive and Negative Affect Scale (PANAS)16 will be used to measure mood. Participants 
will be asked to indicate to what extent they currently experience ten positive and ten 
negative emotions, ranging from (1) ‘very slightly or not at all’ to (5) ‘extremely’. The PANAS 
will be completed before administration of the study drug, three hours after administration 
of the study drug, and following completion of the cognitive tests. 
 
3.2.8 Depressive Symptoms 
The Beck Depression Inventory (BDI-II) 17 and Patient Health Questionnaire (PHQ-9) 18 will 
be used as self-administered measures of depression severity. The PHQ-9 is a briefer 
measure than the BDI-II (9 items versus 21 items), and is more widely used in primary care. 
Conversely, the BDI-II is based on the cognitive theory of depression, and thus better relates 
to the concept of negative self-schemata.  
 
3.2.9 Anxiety 
The Generalised Anxiety Disorder-7 (GAD-7)19 will be used to measure generalised anxiety. 
The GAD-7 is widely used in clinical settings to screen for anxiety disorders. 
 
3.2.10 Social Anxiety 
The Brief Fear of Negative Evaluation (BFNE) Scale will be used at each time-point, as a 
measure of social anxiety 20. This is a 12-item self-report measure of fear of negative 
evaluation by others. 

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3.2.11 Neuroticism 
The Eysenck Personality Questionnaire Abbreviated (EPQR-A) will be used to measure 
neuroticism at baseline21. 
 
3.2.12 State and Trait Anxiety Inventory 
The Trait subscale of the State and Trait Anxiety Inventory (STAI) will be completed at 
baseline only. The State subscale of the STAI will be completed before administration of the 
study drug, three hours after administration of the study drug, and following completion of 
the cognitive tests22. 
 
3.2.13 Visual Analogue Scales 
Visual Analogue Scales (VAS) will be used to measure the subjective states of happiness, 
sadness, disgust, anger, fear, anxiety and alertness. Participants will be asked to place a 
mark on a line to indicate the extent to which they feel each emotion. These will be 
completed before administration of the study drug, three hours after administration of the 
study drug, and following completion of the cognitive tests. 
 
3.2.14 Side Effects Questionnaire 
A short questionnaire will be used to measure side effects of the study drug before 
administration of the study drug, three hours after administration of the study drug, and 
following completion of the cognitive tests. This will determine baseline bodily symptoms 
and changes following administration of the study drug. Participants will be asked to what 
extent they experience the following side effects: nausea, dizziness, dry mouth, headache, 
alert, agitation. 
 
3.3 Indices 
 
3.3.1 Social Evaluation Learning 
An overall index of positive or negative bias will be calculated for each referential condition 
(self, friend, stranger) using errors to criterion. Bias is calculated by subtracting errors to 
criterion made when learning the dislike rule from errors to criterion made when learning 
the like rule. A positive value indicates a negative bias, as fewer errors are made learning 
the dislike rule compared to the like rule. Conversely, a negative value indicates a positive 
bias, as fewer errors are made learning the like rule compared to the dislike rule. 
 
Mean global ratings will be calculated separately for each referential-rule combination block 
(i.e. self-like, self-dislike, friend-like, friend-dislike, stranger-like, stranger-dislike). Overall 
mean ratings for each referential condition will also be generated. As the feedback 
contingencies (% of positive words correct) average to 50% across blocks in each referential 
condition, global ratings above 50% will be considered as a positive bias and those below as 
a negative bias. 
 
Mean perception ratings will be calculated for each referential-rule block, and overall for 
each condition.  
 
3.3.2  Associative Learning 

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Mean accuracy and reaction times will be calculated for each referential condition (self, 
friend, stranger), reward condition (high, medium, low) and valence condition (positive, 
neutral, negative) for each respective task.  
 
3.3.3 Social Cooperation 
The main outcome for this task is the proportion of rounds on which participants choose to 
cooperate. Reaction times for cooperation versus non-cooperation choices will also be 
calculated. The conditional probability of cooperating will be calculated according to the 
proportion of rounds on which participants cooperated following each of the four possible 
outcomes. 
 
3.3.4 Self-Esteem Go/No-Go Task 
Discriminative accuracy (d’) will be calculated through applying Z-score transformations, and 
subtracting hit z-scores from false alarm z-scores. Z-scores are adjusted by adding or 
subtracting .005 if hit or false-alarm rates are 0 or 1. d' –values can then be compared for 
each possible categorical combination to examine implicit self-biases.  
 
3.3.5 Emotional Categorisation and Recall 
The mean number of positive and negative words categorised as describing or not 
describing the participant/the other will be recorded. Mean hits and false intrusions will be 
collected for each referential condition and valence. 
 
3.3.6 Questionnaires 
Scores will be calculated by totalling scales and subscales, following standard procedures for 
each questionnaire. 
 
 
 
 

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4. Design Plan 
 
4.1 Study Type 
Randomised double-blind placebo-controlled parallel-group 
 
4.2 Blinding 
Double-blind 
 
4.3 Study Design 
A parallel group design will be used with study group (citalopram versus placebo) as a 
between-subject factor. 
 
4.4 Randomisation 
Participants will be randomly assigned to receive placebo or citalopram on the day of the 
study visit.  
 
5. Analysis Plan 
 
5.1 Statistical Models 
 
5.1.1 Primary Analyses 
 
H1 Social Evaluation Learning  
Participants administered citalopram will display a positive bias towards the self compared 
to participants administered a placebo, as indicated by fewer errors made before learning 
the like rule compared to the dislike rule. 
 
A mixed-effects linear regression model will be conducted with bias scores as the outcome, 
and referential condition, group, and the interaction between referential condition and 
group as predictors. Subject will be entered as a random effect to account for the within-
subject effect of referential condition. 
 
To further examine whether associations between bias and group are driven by learning 
within a particular rule (e.g. better learning of ‘dislike’ or worse learning of ‘like’), a mixed-
effects linear regression model will be conducted with errors to criterion as the outcome 
and referential condition, rule, group, and the interaction between these variables as 
predictors. Subject will be entered as a random effect to account for the within-subject 
effect of referential condition and rule. 
 
H2 Self Associative Learning 
Participants administered citalopram will show a greater bias towards the self compared to 
those administered a placebo, as measured by faster reaction times and greater accuracy 
when matching neutral shapes to self-related stimuli, than stimuli related to a friend or a 
stranger.  
 
A mixed-effects linear regression model will be conducted with reaction time as the 
outcome, and group, referential condition (self, friend, stranger), and the interaction 

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between group and referential condition as predictors. Subject will be entered as a random 
effect to account for the within-subject effect of condition. This model will be repeated with 
accuracy as the outcome.  
 
5.1.2 Secondary Analyses 
 
H3 Reward Associative Learning 
Participants administered citalopram will show a greater bias towards higher levels of 
reward compared to those administered a placebo, as measured by faster reaction times 
and greater accuracy when matching neutral shapes to high-reward stimuli, than stimuli 
related to medium and low levels of reward.  
 
The model outlined for hypothesis 2 will be repeated with data from the reward associative 
task. Reward condition (high, medium, low), rather than referential condition, will be used 
as a predictor. 
 
H4 Valence Associative Learning 
Participants administered citalopram will show a greater bias towards positive stimuli 
compared to those administered a placebo, as measured by faster reaction times and 
greater accuracy when matching neutral shapes to positive (happy) stimuli, than stimuli 
related to neutral or negative (sad) stimuli.  
 
The model outlined for hypothesis 2 will be repeated with data from the valence associative 
task. Valence condition (happy, neutral, sad), rather than referential condition, will be used 
as a predictor. 
 
H5 Social Cooperation 
Participants administered citalopram will show greater levels of social cooperation 
compared to those administered a placebo, as measured by a greater proportion of 
cooperative behaviours in the prisoner’s dilemma task. 
 
A mixed-effects linear regression model will be conducted with the proportion of rounds 
participants chose to cooperate as the outcome, and group, block (cooperative versus non-
cooperative), and the interaction between these variables as predictors. Subject will be 
entered as a random effect to account for the within-subject effect of block. 
 
H6 Self-Esteem Go/No-Go Task 
Participants administered citalopram will show a greater implicit positive self-esteem 
compared to those administered a placebo, as measured by a greater sensitivity towards 
categorising positive words about the self.  
 
A mixed-effects linear regression model will be conducted with d’ as the outcome, and 
group, referential condition (self vs. other), valence (positive vs. negative), and the 
interaction between these variables as predictors. Subject will be entered as a random 
effect to account for the within-subject effect of condition and valence. This model will be 
repeated separately with hits and false alarms as the outcome. 
 

Page 17 of 20 
 
H7 Emotional Categorisation and Recall 
Participants administered citalopram will categorise a greater number of positive words as 
describing themselves and recall a greater number of positive words about the self 
compared to those administered a placebo 
 
A mixed-effects linear regression model will be conducted with number of words recalled as 
the outcome, and group, referential condition (self vs. other), valence (positive vs. 
negative), and the interaction between these variables as predictors. Subject will be entered 
as a random effect to account for the within-subject effect of condition and valence. This 
model will be repeated separately with number of positive words and number of negative 
words categorised as the outcome. 
 
Baseline differences between groups 
Differences between groups for demographic and baseline measures will be analysed using 
independent t-tests. 
 
Influence of drug administration on mood 
A mixed-effects linear regression model will be conducted for each measure of mood as the 
outcome in separate models. In each model group, timepoint and the interaction between 
these will be entered as predictors. Subject will be entered as a random effect to account 
for the within-subject effect of timepoint. 
 
5.2 Transformations 
Data that deviates from normality will be transformed to a normal 
 
5.3 Follow-up Analyses 
None planned 
 
5.4 Inference Criteria 
Frequentist analyses with an alpha value of 0.05 will be used. 
 
5.5 Data Exclusion 
 
5.5.1 Associative Learning Task 
Responses less than 200 ms will be excluded6. 
 
5.5.2 Self-Esteem Go/No-Go Task 
In accordance with Gregg and Sedikides'11 procedure, participants will be considered non-
compliant and excluded if overall bias scores (average hits + false alarms) are below 12 or 
above 36, and/or discrimination scores (average hits – false alarms) are below 5. 
Participants data will also be removed at the block level if identical responses are made 
throughout the block (e.g. all responses are ‘go’ or all responses are ‘no-go’). 
 
5.6 Missing Data 
If less than 5% of data is missing overall, listwise deletion methods will be used. If greater 
than 5% of data is missing single imputation methods will be used, where the data is 
replaced with the group mean to which the participant belongs (i.e. citalopram versus 

Page 18 of 20 
 
placebo). Participants with data missing from a specific test will be excluded from analyses 
for that particular test, but will be included in other analyses if data are available. 
 
6. Funding Source 
This study is being funded by the National Productivity Innovation Funded awarded to 
Catherine Hobbs at the University of Bath through the GW4 MRC BioMed Doctoral Training 
Programme. 
Recruitment and data collection for this study will take place within the University of Oxford 
Psychopharmacology and Emotion Research Lab.  
 

Page 19 of 20 
 
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