American Journal for Young Scientists ยท ISSN 3068-9015
Targeting Stress-Induced Depression with a Hippocampal-HPA Axis Model and Therapeutical Interventions
Authors: Laasya Munjeti
Published: September 19, 2025
Category: Computational Neuroscience
Abstract
Chronic stress is a well-known cause of depression, largely mediated through dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. In this study, we present a modified minimal model of the HPA axis that integrates two key inhibitory pathways: one representing stress-induced hippocampal neuronal loss, and another capturing the impaired inhibitory feedback from the hippocampus to the hypothalamus. Through simulations, we identify specific model parameters that distinguish between resilient and susceptible individuals, demonstrating how prolonged high stress can lead to significant hippocampal dysfunction, diminished HPA regulation, and sustained elevations in stress hormones. Furthermore, we analyzed EEG biomarkers from patients undergoing TMS therapy for depression. By correlating EEGderived features with model parameters, we identified neurophysiological signatures associated with depression. This integration of patient data with computational modeling provides a mechanistic framework for understanding individual variability in treatment response and offers potential biomarkers for predicting TMS efficacy.