Unmasking Neurodivergence - Cortisol and the HPA-Axis

This working paper proposes that neurodivergence arises from differences in physiological calibration established prenatally through the sequential development of the autonomic nervous system (ANS) and the hypothalamic–pituitary–adrenal (HPA) axis. Within genetically susceptible templates, maternal–foetal cortisol rhythms, placental buffering, foetal placement, and timing of exposure set the developmental tone for stress responsivity, attention, and sensory processing.

Cortisol functions as a developmental signal that shapes neuronal growth, synaptic pruning, and myelination. These early rhythms leave durable imprints on limbic and prefrontal circuits, and on connective-tissue biology through modulation of collagen synthesis. The framework integrates established findings in endocrine regulation, immune and oxidative balance, and dopaminergic function. It positions sex hormones as modulators that buffer or amplify stress-axis calibration and treats connective-tissue phenotype as a somatic expression of the same regulatory history.

The paper concludes with proposed testing models focused on genetically predisposed populations and invites empirical collaboration to evaluate this integrative hypothesis. The framework presents neurodivergence as an outcome of adaptive developmental calibration rather than deficit, encouraging biological precision and clinical respect for human variation. By situating neurodivergence within a physiological calibration spectrum, the Cortisol Signal Fidelity framework offers a foundation for empirical investigation into how temporal hormone dynamics shape neurodevelopmental diversity.