Malamud, Jolanda;
Lewis, Gemma;
Moutoussis, Michael;
Duffy, Larisa;
Bone, Jessica;
Srinivasan, Ramya;
Lewis, Glyn;
(2024)
The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.
Psychological Medicine
pp. 1-13.
10.1017/S0033291724000837.
Preview |
Text
the-selective-serotonin-reuptake-inhibitor-sertraline-alters-learning-from-aversive-reinforcements-in-patients-with-depression-evidence-from-a-randomized-controlled-trial.pdf - Published Version Download (572kB) | Preview |
Abstract
BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. RESULTS: There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. CONCLUSIONS: The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. FUNDING: This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).
| Type: | Article |
|---|---|
| Title: | The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1017/S0033291724000837 |
| Publisher version: | http://dx.doi.org/10.1017/s0033291724000837 |
| Language: | English |
| Additional information: | Creative Common License - CCCreative Common License - BY This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. Copyright Copyright © The Author(s), 2024. Published by Cambridge University Press |
| Keywords: | SSRI, randomized clinical trial, reinforcement learning |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191235 |
Archive Staff Only
 |
View Item |
