Neurobiology of Depression and Serotonin Project


The most commonly known hypothesis in regards to depression’s neurobiological mechanism is the “monoamine hypothesis”, where low serotonin and norepinephrine levels are believed to cause depression.

Serotonin Molecule Diagram

However, since serotonin has never been measured directly in the brain of living human beings, all evidence supporting the hypothesis is circumstantial. Indeed, there are a number of findings that are inconsistent or troubling for the monoamine hypothesis. We have been building an empirical case that the monoamine hypothesis has the wrong direction of association. In other words, we propose that serotonin transmission is enhanced in depression rather than reduced. Similar to the “Cognitive Ecology of Mood” project, we explore the adaptive role of high serotonin in maintaining uninterrupted analytical reasoning and rumination, which are conditions needed for successful solving of complex analytical problems.

Further Reading

Andrews, P. W., Bosyj, C., Brenton, L., Green, L., Gasser, P. J., Lowry, C. A., & Pickel, V. M. (2022). All the brain’s a stage for serotonin: the forgotten story of serotonin diffusion across cell membranes. Proceedings of the Royal Society B289(1986), 20221565.

Andrews, P. W., & Amsterdam, J. D. (2020). A hormetic approach to understanding antidepressant effectiveness and the development of antidepressant tolerance. Psychiatria Polska, 54(6), 1067–1090. https://doi.org/10.12740/PP/120084

Andrews, P. W., Bharwani, A., Lee, K. R., Fox, M. & Thomson, Jr., J. A. (2015). Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience & Biobehavioral Reviews, 51 (April), 164-188. https://doi.org/10.1016/j.neubiorev.2015.01.018

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