Time-limited Moderating Effect of Neuroticism on the Cortisol-Depression Relationship after Physical Injury.

Objective: This study examined whether neuroticism moderates the association between baseline serum cortisol levels and the development of depressive disorder over two years following physical injury. Methods: Adults hospitalized for moderate-to-severe injuries were recruited within one month of trauma and completed baseline assessments of serum cortisol and personality traits. Depressive disorders were evaluated at 3, 6, 12, and 24 months using the Mini-International Neuropsychiatric Interview. Logistic regression models tested the independent and interactive effects of cortisol and neuroticism on depressive disorder at each time point, adjusting for demographic, clinical, and psychosocial covariates. Bonferroni correction was applied for repeated testing across four follow-up assessments. Results: Among 923 participants, 239 (25.9%) developed depressive disorder at least once during follow-up. Neither cortisol nor neuroticism independently predicted depressive disorder; however, their interaction was significant specifically at the 3-month post-injury assessment, indicating that individuals with higher neuroticism and lower cortisol were at increased early risk. Interaction terms at 6 and 12 months did not survive multiple comparison correction. Serum cortisol and neuroticism were modestly and inversely correlated. Conclusion: A time-limited interaction between low cortisol and high neuroticism predicted early depressive disorder after physical injury. These findings highlight a transient window in which personality-dependent modulation of hypothalamic- pituitary-adrenal axis function may confer vulnerability, underscoring the importance of early identification and targeted support for high-risk individuals.