Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide, often characterized by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired social affiliation. Despite standard pharmacological treatments, a significant proportion of patients continue to struggle with treatment-resistant depression, necessitating the exploration of effective adjunctive strategies such as animal-assisted interventions (AAIs). The primary objective of this narrative review is to synthesize current neurobiological evidence regarding the efficacy of AAIs in MDD populations. Specifically, we aim to evaluate the modulation of cortisol and oxytocin as primary biomarkers and to delineate the role of C-tactile (CT) afferent pathways in mediating these physiological shifts. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science (2000-2026), focusing on quantitative studies and meta-analyses investigating neuroendocrine responses to AAIs in depressive or high-stress populations. The evidence indicates that even brief (10-20 minute) interactions with animals can lead to a significant reduction in salivary cortisol levels, suggesting rapid HPA axis stabilization. Furthermore, oxytocin secretion, stimulated by visual and tactile contact, enhances emotional regulation. This process is further mediated by the activation of CT-tactile afferents during petting, which project to the insular cortex to promote anxiolytic effects. Comparative analysis suggests that while canine-assisted interventions yield acute stress reduction, equine-assisted therapies may influence long-term diurnal cortisol rhythms. AAIs offer a measurable, biologically grounded supportive treatment for MDD. While promising, the field requires standardized protocols and large-scale longitudinal studies to establish evidence-based guidelines for clinical psychiatric practice.