Key result
High neuroticism linked to ~9% greater risk of developing a first neuroticism-related disease.
Why the study?
Most research on neuroticism and health outcomes has focused on single disorders with controversial findings regarding mortality risk, leaving disease trajectories unclear.
Does high neuroticism affect the risk of future disease and mortality in adults?
Cohort (n=483,916)
Does high neuroticism affect the risk of future disease and mortality in adults?
Hazard Ratio: 1.09 (95% CI 1.05–1.13)
p-value: p=<0.001
High neuroticism increases the risk of developing multiple diseases but paradoxically decreases the risk of all-cause mortality, particularly in patients with multimorbidity.
High neuroticism may accelerate disease onset yet lower mortality in multimorbidity; leaves open causal roles and need for prospective trials.
BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION: This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
No takes yet. Share an insight, caveat, or question.
Huang et al. (2025) conducted a cohort in General population (n=483,916). High neuroticism vs. Lower neuroticism was evaluated on Transitions from a healthy state to a first neuroticism-related disease (HR 1.09, 95% CI 1.05-1.13, p=<0.001). High neuroticism was associated with an increased risk of transition from a healthy state to a first neuroticism-related disease (HR 1.09; 95% CI 1.05-1.13; P<0.001).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: