Dehydroepiandrosterone sulfate (DHEA-S), cortisol, and adrenocorticotropic hormone (ACTH) levels in drug-naïve, first-episode patients with psychosis

The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in regulating dopamine activity in specific brain areas, particularly in the limbic system, as well as in the stress response. The assessment of the HPA axis is important for the research of biological mechanisms leading from stressful experiences to the onset of psychosis. The release of adrenocorticotropic hormone (ACTH) by the anterior pituitary stimulates the production of cortisol and Dehydroepiandrosterone (DHEA) by the adrenal cortex as a response to stress. The co-release of DHEA may act as a protective mechanism against the damaging effects of excessive cortisol activity. We aimed to measure and compare serum DHEA-S, as well as ACTH, cortisol levels, and cortisol/DHEA-S ratio in drug-naïve FEP patients and matched controls. Data were included for 110 subjects (70 men and 40 women), comprising 55 patients and 55 controls. The mean age was 31.3 years (SD 8.7) in patients and 31.4 years (SD 8.9) in controls. Serum DHEA-S was higher in patients compared to controls [0.69 (0.40) versus 0.50 (0.19), respectively]. Serum ACTH was similar between patients and controls [28.0 pg/ml (6.2-73.9) versus 22.4 pg/ml (7.0-70.5), respectively]. Serum cortisol levels and cortisol/DHEA-S ratio were lower in patients [12.6 μg/dl (4.5) and 4.4% (1.3-19.5), respectively] compared to controls [15.4μg/dl (3.7) and 7.0% (2.4-25.5), respectively]. Sub-analysis revealed that in men, serum DHEA-S was similar between male patients and controls [0.53 (0.23) versus 0.48 (0.17), respectively], whereas in women, serum DHEA-S was higher in patients compared to controls [0.97 (0.47) versus 0.55 (0.20), respectively]. ACTH levels were not different in the above subgroups. Serum cortisol in men was lower in patients compared to controls [12.8 μg/dl (4.4) versus 15.9 μg/dl (3.6)]. Additionally, the cortisol/DHEA-S ratio was lower in patients compared to controls in men [4.4% (1.3-19.5) versus 5.8% (2.4-15.4)], as well as in women [4.3% (1.8-15.2) versus 7.9% (4.0-25.5), respectively]. Correlation analysis was performed to examine the association between different psychopathological characteristics in patients and measured hormones. It was found that the PANSS cognitive subscale was positively correlated with DHEA-S in men and the PANSS positive subscale was negatively correlated with DHEA-S in women. In the linear regression analysis, DHEA-S was positively associated with the PANSS cognitive subscale in men.