An investigation into serotonergic and environmental interventions against depression in a simulated delayed reward paradigm
Bernd Porr, Alex Trew, Alice Miller
bioRxiv Preprint Server April 4, 2019 preprint DOI: 10.1101/580456 via bioRxiv
Summary
A computational model of the limbic system compares two pharmacological approaches to treating depression: SSRIs, which increase serotonin accumulation, and psychedelics, which stimulate excitatory serotonin receptors. The model simulates a delayed reward paradigm disrupted by low serotonin. Low serotonin allows small signals to pass through decision-making neurons, while high serotonin blocks smaller signals but amplifies larger ones. Behavioral simulations and model checking show SSRIs perform significantly better than psychedelics in this paradigm. However, psychedelics might be more effective in situations where high exploration is beneficial for obtaining rewards.
Study at a glance
| Characteristics | Computational modeling study |
|---|---|
| Citations | 1 |
| Key finding | SSRIs perform significantly better than psychedelics in a simulated delayed reward paradigm, though psychedelics may be more effective in exploration-beneficial contexts. |
Abstract
The disruption of the serotonergic (5HT) system has been implicated in causing major depression and the standard view is that a lack of serotonin is to blame for the resulting symptoms. Consequently, pharmacological interventions aim to increase serotonin concentration in its target areas or stimulating excitatory 5HT receptors. A standard approach is to use serotonin reuptake inhibitors (SSRIs) which cause a higher accumulation of serotonin. Another approach is to stimulate excitatory serotonin receptors with psychedelic drugs. This paper compares these two approaches by first setting up a system level limbic system model of the relevant brain areas and then modelling a delayed reward paradigm which is known to be disrupted by a lack of 5HT. Central to our model is how serotonin changes the response characteristics of decision making neurons where low levels of 5HT allows small signals to pass through whereas high levels of 5HT create a barrier for smaller signals but amplifying larger ones. We show with both standard behavioural simulations and model checking that SSRIs perform significantly better against interventions with psychedelics. However, psychedelics might work better in other paradigms where a high level of exploration is beneficial to obtain rewards.