Sex differences in the association between basal serum cortisol concentrations and cortical thickness

Basal cortisol concentrations vary between men and women. Likewise, previous findings suggest stress-related cortical thickness alterations. Thus, we aimed at elucidating sex differences in the association between serum cortisol concentrations and cortical thickness.

Data of 2594 participants (55.55% male; mean age = 53.55 years ± 13.17 years) of the general population were used to investigate sex differences in basal serum cortisol concentrations and associations of serum cortisol concentrations with global and regional cortical thickness. The validity of the results was tested by including sex hormone concentrations as a biological and childhood maltreatment and depressive symptoms as a psychological confounder.

Basal serum cortisol concentrations were higher in men than in women (β = -0.158, t₍₂₅₇₅₎ = -6.852, p = 9.056e-12). Sex differences in serum cortisol concentrations were diminished by including serum concentrations of testosterone, estrone, or estradiol in the models. In men but not in women, serum cortisol concentrations were inversely associated with the global cortical thickness (men: β = -0.064, t₍₁₄₁₂₎ = -3.010, p = .003; women: β = -0.016, t₍₁₁₃₁₎ = -0.607, p = .544). Additionally, these effects were observed in eleven cortical regions after adjusting for multiple testing. The associations were independent of childhood maltreatment and depressive symptoms.

Sex differences in serum cortisol concentrations and the association between serum cortisol concentrations and cortical thickness suggest important sex-specific effects of stress on the brain. Future studies should integrate the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis in sex-stratified analyses.