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Figure 4 | Theoretical Biology and Medical Modelling

Figure 4

From: Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

Figure 4

Results obtained for all the runs performed with the model generated by a Boolean approximation using Synchronous Boolean Networks (SBNs). Nodes related to G-protein signaling are not shown. An input vector of ones was used for all nodes except the SSRI and stress nodes, which were activated or deactivated to generate 4 possible simulations. A. The pattern obtained when stress and SSRI were both in the ‘off’ state (basal system) and the other nodes were ‘on’. B. The effect of SSRI activity on the serotonin regulation pathway under unstressed conditions is shown. Notice that the antidepressant activity blocks 5-HTT and 5-HT1A*, causing 5-HT synthesis, degradation and transport pathways to remain active. C. The pattern generated when the stress node is ‘on’ and SSRI is ‘off’. In this case, a cyclical pattern was observed for nodes related to 5-HT synthesis, transportation and degradation. This figure also shows that while the stress response is well regulated, a persistent stressed state activates the HPA axis over time. D. SSRI clearly regulates the cyclical pattern shown in C, but it does not cause the same pattern shown in B. This is in line with expectation and demonstrates that SSRIs do not have any effect when the patient is stressed.

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