Is chronic insomnia a 24-hour hyperarousal state linked to autonomic and HPA axis activation?

Chronic insomnia is increasingly understood as a persistent, 24-hour hyperarousal state driven by reciprocal dysregulation of autonomic and endocrine pathways.

Mechanistic explanations

• Autonomic dysregulation: Insomnia involves a state of physiologic hyperarousal marked by increased sympathetic nervous system tone and reduced parasympathetic (vagal) activity. This autonomic shift manifests as elevated pre-sleep heart rates and decreased heart rate variability (HRV), particularly during the sleep onset period.
• HPA axis hyperactivation: Hyperarousal is further driven by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. This neuroendocrine shift increases the secretion of wake-promoting mediators, including corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, which directly oppose sleep-promoting mechanisms and disrupt sleep architecture.

Clinical implications & limitations

• Limitations of single-point testing: A single early-morning cortisol measurement is highly vulnerable to transient confounding variables (such as exact waking time, acute stress, and sleep duration) and displays poor day-to-day stability.
• Missed diurnal patterns: Single-point morning tests cannot capture the dynamic diurnal cortisol rhythm, which naturally peaks shortly after waking and declines to a nadir at bedtime. Individuals with sleep disturbances or chronic stress frequently present with abnormal diurnal variations, such as flattened diurnal slopes or elevated evening cortisol, despite having normal or highly variable morning values. Multi-point diurnal sampling (e.g., salivary testing across 4–5 time points) is necessary to reliably characterize these curves.

Bottom line

• Chronic insomnia is strongly associated with physiologic hyperarousal, presenting as heightened sympathetic tone and HPA axis activation, which cannot be reliably detected by a single morning cortisol measurement; comprehensive assessment of these dynamic endocrine patterns requires multi-point diurnal salivary monitoring.