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Meta-Analysis
. 2022 Apr 1;79(4):313-322.
doi: 10.1001/jamapsychiatry.2022.0051.

Reinforcement Learning in Patients With Mood and Anxiety Disorders vs Control Individuals: A Systematic Review and Meta-analysis

Affiliations
Meta-Analysis

Reinforcement Learning in Patients With Mood and Anxiety Disorders vs Control Individuals: A Systematic Review and Meta-analysis

Alexandra C Pike et al. JAMA Psychiatry. .

Abstract

Importance: Computational psychiatry studies have investigated how reinforcement learning may be different in individuals with mood and anxiety disorders compared with control individuals, but results are inconsistent.

Objective: To assess whether there are consistent differences in reinforcement-learning parameters between patients with depression or anxiety and control individuals.

Data sources: Web of Knowledge, PubMed, Embase, and Google Scholar searches were performed between November 15, 2019, and December 6, 2019, and repeated on December 3, 2020, and February 23, 2021, with keywords (reinforcement learning) AND (computational OR model) AND (depression OR anxiety OR mood).

Study selection: Studies were included if they fit reinforcement-learning models to human choice data from a cognitive task with rewards or punishments, had a case-control design including participants with mood and/or anxiety disorders and healthy control individuals, and included sufficient information about all parameters in the models.

Data extraction and synthesis: Articles were assessed for inclusion according to MOOSE guidelines. Participant-level parameters were extracted from included articles, and a conventional meta-analysis was performed using a random-effects model. Subsequently, these parameters were used to simulate choice performance for each participant on benchmarking tasks in a simulation meta-analysis. Models were fitted, parameters were extracted using bayesian model averaging, and differences between patients and control individuals were examined. Overall effect sizes across analytic strategies were inspected.

Main outcomes and measures: The primary outcomes were estimated reinforcement-learning parameters (learning rate, inverse temperature, reward learning rate, and punishment learning rate).

Results: A total of 27 articles were included (3085 participants, 1242 of whom had depression and/or anxiety). In the conventional meta-analysis, patients showed lower inverse temperature than control individuals (standardized mean difference [SMD], -0.215; 95% CI, -0.354 to -0.077), although no parameters were common across all studies, limiting the ability to infer differences. In the simulation meta-analysis, patients showed greater punishment learning rates (SMD, 0.107; 95% CI, 0.107 to 0.108) and slightly lower reward learning rates (SMD, -0.021; 95% CI, -0.022 to -0.020) relative to control individuals. The simulation meta-analysis showed no meaningful difference in inverse temperature between patients and control individuals (SMD, 0.003; 95% CI, 0.002 to 0.004).

Conclusions and relevance: The simulation meta-analytic approach introduced in this article for inferring meta-group differences from heterogeneous computational psychiatry studies indicated elevated punishment learning rates in patients compared with control individuals. This difference may promote and uphold negative affective bias symptoms and hence constitute a potential mechanistic treatment target for mood and anxiety disorders.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Pike and Robinson report salary support from a Medical Research Council senior nonclinical fellowship during the conduct of the study, awarded to Dr Robinson, and a Medical Research Council Proximity-to-Discovery award with Roche, who have provided in-kind contributions regarding work on heart rate variability and anxiety and have sponsored travel outside of the submitted work. Dr Robinson reports that his senior nonclinical fellowship is partially in collaboration with Cambridge Cognition (who plan to provide in-kind contribution); he is also running an investigator-initiated trial with medication donated by Lundbeck (escitalopram and placebo; no financial contribution); has completed consultancy work on affective bias modification for Peak, online cognitive behavioral therapy for Ieso Digital Health, and on randomized clinical trials for anxiety for Roche; Dr Robinson also sits on the committee of the British Association of Psychopharmacology. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Procedure
Note that the methods used in (5) were maximum a posteriori (MAP) with either 1 prior across all participants (MAP; 1) or separate priors for each group (MAP; 2); or variational bayesian analysis (VBA) with 1 prior (VBA; 1) or separate group priors (VBA; 2).
Figure 2.
Figure 2.. Forest Plots for the Conventional Meta-analysis Comparing Learning Rate and Inverse Temperature
The figure shows standardized mean differences (Hedges g) between patients and control individuals. Where the relevant parameter was not included in the original article, the standardized mean difference is marked as not applicable (NA). SMD indicates standardized mean difference.
Figure 3.
Figure 3.. Forest Plots for the Conventional Meta-analysis Comparing Reward Learning Rate and Punishment Learning Rate
The figure shows standardized mean differences (Hedges g) between patients and control individuals. Where the relevant parameter was not included in the original article, the standardized mean difference is marked as not applicable (NA). SMD indicates standardized mean difference.
Figure 4.
Figure 4.. Forest Plots of the Cohen d Effect Sizes for the 4 Most Highly Represented Parameters From the Simulation Meta-analysis
Fixed-effects meta-analyses were performed over the different analytic approaches. Each effect size represents a different analytic approach. Note that 95% CIs are not visible here as they overlap with the effect sizes. MAP indicates maximum a posteriori analysis; VBA, variational bayesian analysis.

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