Salivary glucocorticoid receptor gene DNA methylation and cortisol output in relation to lifestyle, psychological distress, and cognition in university students.
BACKGROUND University students often experience high psychosocial stress and lifestyle irregularities that may affect hypothalamic-pituitary-adrenal axis regulation and epigenetic regulation of the glucocorticoid receptor gene (NR3C1). This study examined associations of lifestyle factors with peripheral NR3C1 DNA methylation and cortisol output, and their relationships with psychological distress and cognitive function. METHODS A cross-sectional study included 97 university students (48 women; mean age = 21.6 years). Salivary NR3C1 promoter methylation was measured by pyrosequencing, and two components (C1, C2) were derived. Salivary cortisol area under the curve with respect to ground (AUCg) was calculated. Lifestyle behaviors, cardiorespiratory fitness (CRF), symptoms of depression, anxiety, and stress, and cognitive domains were assessed. Multiple regression and moderation analyses tested associations and interactions with sex and BMI. RESULTS In uncorrected analyses, higher sedentary behavior was associated with lower NR3C1 C2 scores, and higher physical activity and CRF were related to lower cortisol AUCg. Higher NR3C1 C1 scores were associated with poorer executive function and inhibition, and cortisol AUCg was positively associated with depressive symptoms. However, none of these associations survived correction for multiple comparisons. Exploratory analyses indicated that higher NR3C1 C2 scores were associated with better attention at lower BMI and better attention-processing speed in women, whereas higher NR3C1 C1 scores were associated with poorer inhibition in men. CONCLUSIONS Nominal findings suggest movement-related behaviors as the clearest lifestyle correlates of stress-system markers. Moderation analyses suggest sex- and BMI-related heterogeneity in selected cognition-methylation associations. These findings require confirmation in adequately powered studies.