American Journal for Young Scientists · ISSN 3068-9015
Neuroendocrine Regulation of Mirror Neurons: Linking Hypothalamic–Pituitary–Thyroid Axis Dysfunction to Autism
Authors: Annika Pathak, Disha Chhabra
Published: October 23, 2025
Category: Computational Neuroscience
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction, communication, and restricted or repetitive behaviors. One promising line of research points to dysfunction in the mirror neuron system, which normally supports imitation, empathy, and understanding of others’ actions. Despite its potential importance, the biological basis of mirror neuron impairment remains poorly understood. Here, we propose that dysregulation of the hypothalamic–pituitary–thyroid (HPT) axis provides a mechanistic link between endocrine imbalance and mirror neuron dysfunction, thereby contributing to the social and cognitive deficits observed in ASD. To explore this idea, we developed a minimal mathematical model that couples HPT axis dynamics with mirror neuron activity. The model integrates classical feedback regulation of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and thyroid hormones (T3/T4), with an additional term describing thyroid-dependent mirror neuron growth. Simulations revealed that acute suppression of HPT input leads to transient decreases in thyroid hormone levels and mirror neuron activity, whereas chronic suppression produces sustained impairments that persist even after endocrine input is restored. Phase-space analysis showed that mirror neuron maturation is highly sensitive to thyroid hormone thresholds, indicating that small endocrine fluctuations can have disproportionate neural effects. Furthermore, we identified two pituitary dysfunction pathways—reduced cell production and accelerated cell removal—that both converge on diminished T3/T4 availability and impaired mirror neuron function. Finally, we linked these endocrine effects to metabolic vulnerability by highlighting reduced succinate dehydrogenase activity in the Krebs cycle as a factor that could further compromise neural energy balance. Together, these findings suggest that systemic thyroid and metabolic regulation plays a critical role in shaping neural circuits underlying social cognition and may represent a key axis of vulnerability in ASD.