Better sleep quality is associated with a lower risk of psychiatric disorders among individuals with preclinical obesity, with 16 plasma proteins identified as significant partial mediators of this association.
Key Findings
Results
Higher composite sleep scores were associated with significantly lower risk of psychiatric disorders in individuals with preclinical obesity, with the lowest risk observed in the highest sleep score group.
Study included 91,380 participants with preclinical obesity from the UK Biobank prospective cohort
Participants were categorized into six groups according to sleep scores
Using Group 1 (lowest sleep score) as reference, Group 6 (highest sleep score) showed fully adjusted HR = 0.47 (95% CI: 0.33–0.67)
Risk of psychiatric disorders decreased significantly across Groups 2–6 with increasing sleep score
Mean follow-up period was 12.9 years, during which 8,992 incident cases of psychiatric disorders were observed
Results
The inverse association between composite sleep score and psychiatric disorder risk was significant for specific psychiatric disorders, with the most notable effect observed for attention deficit hyperactivity disorder (ADHD).
ADHD showed the most notable effect with fully adjusted HR = 0.24 (95% CI: 0.08–0.72) for the highest vs. lowest sleep score group
Inverse associations remained significant after full adjustment across analyses of specific psychiatric disorders
Multiple Cox proportional hazards regression analysis was used to estimate HRs for incidence risk
Results
Sixteen plasma proteins were identified as significant partial mediators of the association between composite sleep score and psychiatric disorder risk in individuals with preclinical obesity.
Mediation analysis of plasma proteomics was conducted in a subset of 9,486 participants
All 16 identified proteins exerted significant partial mediating effects
The proteomic analysis was intended to illuminate underlying biological mechanisms linking sleep quality to psychiatric disorder risk in preclinical obesity
Background
The study population consisted of individuals with preclinical obesity, a group known to be at higher risk for several psychiatric disorders.
Preclinical obesity was the defining inclusion criterion for the 91,380 participants
Obesity is associated with higher risk of several psychiatric disorders, motivating the focus on this subpopulation
The study prospectively followed participants over a mean of 12.9 years
What This Means
This research suggests that people with preclinical obesity (a stage of obesity before significant health consequences emerge) who have better sleep quality face a substantially lower risk of developing psychiatric disorders over time. Using data from nearly 91,400 UK Biobank participants followed for almost 13 years, the researchers found that those with the highest composite sleep scores had roughly half the risk of developing psychiatric disorders compared to those with the poorest sleep scores. The strongest protective effect was seen for attention deficit hyperactivity disorder (ADHD), where those with the best sleep scores had about one-quarter the risk of developing ADHD compared to those with the worst sleep scores.
The study also examined the biological 'pathway' between sleep and psychiatric health by analyzing proteins in participants' blood. Sixteen specific plasma proteins were found to partially mediate — or help explain — the link between sleep quality and psychiatric disorder risk, suggesting there are measurable biological mechanisms through which sleep affects mental health in this population.
This research suggests that assessing and improving sleep may be a meaningful strategy for reducing psychiatric disorder risk in people with preclinical obesity. The identification of specific proteins that connect sleep quality to psychiatric outcomes could also open avenues for future research into biological targets for intervention, though further studies would be needed to confirm causality and clinical applicability.
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Xu M, Cao W, Sun H, Lu S, Shen Y, Hu G. (2026). Composite sleep score and risk of psychiatric disorders via proteomic features in preclinical obesity: a prospective cohort study from the UK Biobank.. Epidemiology and psychiatric sciences. https://doi.org/10.1017/S2045796026101024