Sex-specific associations between insomnia symptoms and mental health among Chinese young adults and the modified effect of CRY2 gene DNA methylation.

Background: The prevalence of insomnia and mental illness varies by sex. The mRNA expression level of the CRY gene in patients with insomnia is significantly decreased, and the expression level of the CRY2 gene is closely related to depression. However, sex differences in the link between insomnia and symptoms of anxiety, depression, and stress, as well as whether CRY2 gene DNA methylation can regulate this association, are not yet fully understood.

Objective: Investigate sex-specific differences in the associations between insomnia symptoms and symptoms of anxiety, depression, and stress among young adults. Furthermore, we explored whether the CRY2 clock DNA methylation moderates these relationships.

Methods: A total of 1100 participants from two Chinese universities provided baseline data on insomnia symptoms and follow-up symptoms of anxiety, depression, and stress assessments 1 year later. Among them, 605 participants contributed DNA methylation data for the CRY2 gene. Binary logistic regression and restricted cubic spline models were employed to analyze both linear and nonlinear relationships. Moderation analyses examined the effect of CRY2 gene DNA methylation, complemented by stratified analyses for sex-specific differences.

Results: Significant sex-specific differences emerged in recognizing symptoms of anxiety, depression, and stress, with insomnia symptoms notably increasing the risk of symptoms of anxiety, depression, and stress. Logistic regression revealed a significant association between insomnia symptoms and symptoms of anxiety, depression, and stress exclusively in females. Furthermore, restricted cubic spline analyses demonstrated a consistent nonlinear relationship in both males and females. Notably, CRY2 gene DNA methylation negatively moderated the relationship between insomnia symptoms and symptoms of anxiety, depression, and stress, and had sex-specific difference.

Conclusion: Elevated insomnia symptoms at baseline correlated with an increased risk of symptoms of anxiety, depression, and stress after 1 year, with significant sex differences observed. Logistic regression revealed that this association was significant only in females, although a consistent nonlinear pattern was seen in both sexes. Furthermore, CRY2 gene DNA methylation acted as a negative moderator of this relationship. These results highlight the necessity of an early monitoring strategy for females incorporating epigenetic factors.