Insomnia shows up in the blood: higher cortisol and simmering inflammation

Insomnia is increasingly viewed not as a purely psychological complaint but as a systemic disorder, involving persistent hyperarousal, neuroendocrine dysregulation, immune activation and impaired stress adaptation. If that framing is right, the condition should leave measurable traces in the blood. Yet the scattered studies on circulating biomarkers in insomnia had never been comprehensively pulled together, leaving it unclear which signals are robust and which are noise. This review set out to synthesise that evidence and ask what the blood of a person with insomnia actually looks like compared with a healthy sleeper.

The researchers conducted a systematic review and pooled analysis of studies that compared circulating biomarkers between adults with insomnia and healthy controls. Thirty-two studies qualified, together covering 4578 individuals with insomnia and 28382 healthy controls. Differences between groups were pooled statistically, with subgroup and sensitivity analyses run to check how robust each result was, and the certainty of the evidence was formally graded. The biomarkers spanned stress hormones, inflammatory molecules and markers linked to brain and nerve function.

The standout result was cortisol, which was substantially elevated in people with insomnia. A cluster of inflammatory markers, including IL-6, TNF-α, C-reactive protein, IL-1β, IL-2 and IFN-γ, was also significantly increased, while the anti-inflammatory markers IL-4 and IL-10 showed no difference. Neuropeptide Y, described by the authors as relevant to stress-buffering capacity, was significantly reduced. Notably, corticotropin-releasing hormone and BDNF showed no significant pooled differences, and TNF-α, IL-1β, IL-6, CRP and neuropeptide Y held up consistently when the analyses were stress-tested.

These findings support the emerging picture of insomnia as a whole-body condition involving an overactive stress hormone system, low-grade systemic inflammation and possibly a weakened capacity to buffer stress. Because every included study compared groups at a single point rather than intervening, the direction of the relationship remains open: insomnia could drive the biology, the biology could drive the insomnia, or a third factor could drive both. The authors frame the biomarker pattern as a foundation for future work on biologically stratifying insomnia, which is a research goal rather than a clinical reality today.

If you struggle with persistent insomnia, this is a reason to think of it as something your whole body participates in, not a failing of willpower or a purely mental habit. The consistent link with cortisol and inflammatory markers helps explain why chronic poor sleep so often travels with feeling physically run down. It does not mean a blood test can diagnose insomnia, and it does not prove that fixing sleep would lower these markers, since no one here was treated. But it is a solid argument for taking long-running sleep problems seriously rather than shrugging them off.