Emotional bias training as a treatment for anxiety and depression: evidence from experimental medicine studies in healthy and medicated samples

Background Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs. Methods We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up. Results In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains. Conclusions These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression.


SUPPLEMENTARY MATERIAL Supplementary Tables
. Schematic of a training block trial in the emotional bias training task.
An example trial during the training (second) block of an EBT session. Participants respond to a series of emotional faces, categorising each as "happy" or "sad", and receive immediate feedback as to whether this was "Correct" or "Incorrect". In the active condition, this feedback is tailored to train the participant to perceive an additional 2 faces as "happy" in comparison to their responses in the baseline block. In the sham condition, this feedback is matched to their baseline responses (i.e. no training is administered). Analysed (n = 104) ¨ Excluded due to incomplete data (n = 6) ¨ Excluded due to S1 balance point (n = 2) ¨ Excluded due to not providing SSRI (n = 2) Lost to follow-up (n = 11) Completed Session 1 Sham EBT (n = 184) Lost to follow-up (n = 16) Completed Session 1 Active EBT (n = 217) Analysed (n = 108) ¨ Excluded due to incomplete data (n = 8) ¨ Excluded due to S1 balance point (n = 2) ¨ Excluded due to not providing SSRI (n = 1)

Effort Expenditure for Reward Task (EEfRT)
The EEfRT is designed as an objective cognitive measure of anhedonia that measures the amount of physical effort an individual is willing to expend in order to earn a reward (Treadway, Buckholtz, Schwartzman, Lambert, & Zald, 2009). Participants were given a choice between 'easy' and 'hard' trials in return for different monetary rewards. The easy trials required the participant to tap the spacebar repeatedly, while the hard trials required participants to press four keys in sequence: 'Q', 'C', 'M' and 'P'. We adapted the 'hard' trials from the original task (which required participants to press the space bar with their little finger) to account for the present study being conducted remotely, and therefore participants adherence to task instructions could not be monitored (i.e., participants could evade hard trials by using their index finger).
The number of presses required to fill the bar depended on the participant's performance in a brief calibration phase (framed as a practice phase), which took place before the task began. In this phase, participants had to attempt 4 trials, each requiring them to 'fill a bar' that requires a different number of button presses within 21 seconds, using the hard trial button sequence. We recorded the average number of button presses per second in the second and third of these trials, and used this to determine the maximum possible number of presses the participant could have achieve within 21 seconds. Based on pilot experiments, we then increased this value by 15%, thus ensuring that the hard trials were truly difficult and required significant effort to complete. This value was then used as the required number of presses in the following hard trials, with the caveat that we set the maximum required presses at 300, and the minimum at 50. Practice trial four also required this many button presses, to give the participant an indication as to the difficulty of the trials they would face. In contrast, easy trials required 15% of the hard trial button presses, with a minimum of 20 and a maximum of 30.
A trial was considered successful when a participant filled up the bar on the screen to the red line by repeatedly pressing buttons, however this did not guarantee the participant a reward. Hard trials were always worth more than easy trials (15p), but both types of trial came with a shared probability cue (12%, 50%, or 88%), which indicated the likelihood of receiving a reward if the participant successfully fills the bar to the red line ( Figure S4). Upon filling the bar, the participant was presented with a spinner; if the arrow landed in the green segment, the reward in the trial was won. If participants won at least 5 trials, two of the rewards from these trials were selected at random as real 'bonus money' to their study compensation. Figure S4. Example Trial of the Effort-Expenditure for Rewards Task Figure S5. Study 1 (healthy participants) mean emotional balance point at each session, stratified by EBT condition and mental health symptoms. Means are from the baseline (pre-training) block of that EBT session. Sessions 1-4 were completed within a 10-day period. Session 5 was completed approximately 2 weeks after Session 4. Left: Participants are stratified by high and low trait anxiety (high: STAI-Y2 >44). Right: Participants are stratified by depressive symptoms (with symptoms: PHQ-9 >4).