Ruffini, GiulioCastaldo, FrancescaLopez-Sola, EdmundoSanchez Todo, RoserVohryzek, Jakub2025-05-292025-05-292024Ruffini G, Castaldo F, Lopez-Sola E, Sanchez-Todo R, Vohryzek J. The algorithmic agent perspective and computational neuropsychiatry: from etiology to advanced therapy in major depressive disorder. Entropy (Basel). 2024 Nov;26(11):953. DOI: 10.3390/e261109531099-4300http://hdl.handle.net/10230/70556Major Depressive Disorder (MDD) is a complex, heterogeneous condition affecting millions worldwide. Computational neuropsychiatry offers potential breakthroughs through the mechanistic modeling of this disorder. Using the Kolmogorov theory (KT) of consciousness, we developed a foundational model where algorithmic agents interact with the world to maximize an Objective Function evaluating affective valence. Depression, defined in this context by a state of persistently low valence, may arise from various factors—including inaccurate world models (cognitive biases), a dysfunctional Objective Function (anhedonia, anxiety), deficient planning (executive deficits), or unfavorable environments. Integrating algorithmic, dynamical systems, and neurobiological concepts, we map the agent model to brain circuits and functional networks, framing potential etiological routes and linking with depression biotypes. Finally, we explore how brain stimulation, psychotherapy, and plasticity-enhancing compounds such as psychedelics can synergistically repair neural circuits and optimize therapies using personalized computational models.application/pdfeng© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/e26110953Algorithmic information theoryComputational neuroscienceDepressionKolmogorov theory of consciousnessBiotypesBrain stimulationtDCSArtificial intelligenceFree energy principleDigital twinsinfo:eu-repo/semantics/openAccess